preeclampsia novel insights from global rna profiling of trophoblast subpopulations

Accepted Manuscript Preeclampsia: Novel Insights from Global RNA Profiling of Trophoblast Subpopulations Mr Matthew Gormley, BS, Ms Katherine Ona, BS, Miko Kapidzic, MD, Tamara Garrido-Gomez, PhD, Tamara Zdravkovic, PhD;, Susan J Fisher, PhD PII: S0002-9378(17)30441-6 DOI: 10.1016/j.ajog.2017.03.017 Reference: YMOB 11588 To appear in: American Journal of Obstetrics and Gynecology Received Date: 19 January 2017 Revised Date: 15 March 2017 Accepted Date: 17 March 2017 Please cite this article as: Gormley M, Ona K, Kapidzic M, Garrido-Gomez T, Zdravkovic T, Fisher SJ, Preeclampsia: Novel Insights from Global RNA Profiling of Trophoblast Subpopulations, American Journal of Obstetrics and Gynecology (2017), doi: 10.1016/j.ajog.2017.03.017 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain ACCEPTED MANUSCRIPT Preeclampsia: Novel Insights from Global RNA Profiling RI PT of Trophoblast Subpopulations Mr Matthew GORMLEY, BS; Ms Katherine ONA, BS; Miko KAPIDZIC, MD; Tamara GARRIDO-Gomez, PhD; Tamara ZDRAVKOVIC, PhD; and Susan J SC FISHER, PhD M AN U Center for Reproductive Sciences, Department of Obstetrics, Gynecology, and Reproductive Sciences, The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research and the Department of Anatomy, University of California San Francisco, San Francisco, CA (USA) (Mr Gormley, Ms Ona and Drs Kapidzic, Garrido-Gomez, Zdravkovic, and TE D Fisher) This study was funded by R37HD076253 to S.F EP The authors report no conflicts of interest Corresponding author: S.J Fisher, PhD 35 Medical Center Way, Box 0665, San AC C Francisco, CA (USA), telephone (415) 476-5297, fax (415) 476-1635, email susan.fisher@.ucsf.edu Word Count 7395 ACCEPTED MANUSCRIPT CONDENSATION AND SHORT VERSION OF TITLE Brief Summary Global profiling of trophoblast subpopulations isolated by laser microdissection dysregulation in this syndrome Short Title AC C EP TE D M AN U RNA Misexpression in Severe Preeclampsia SC RI PT from the placentas of severe preeclampsia cases revealed novel aspects of RNA ACCEPTED MANUSCRIPT ABSTRACT BACKGROUND: The maternal signs of preeclampsia, including the new onset of high blood pressure, can occur secondary to faulty placentation We theorized RI PT that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis OBJECTIVE: Our goal was to enrich syncytiotrophoblasts, invasive SC cytotrophoblasts or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases Total RNA was subjected to global transcriptional profiling M AN U to identify RNAs that were misexpressed as compared to controls STUDY DESIGN: This was a cross-sectional analysis of placentas from women diagnosed with severe preeclampsia Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection Laser TE D microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts or endovascular cytotrophoblasts Following RNA isolation, a microarray approach was used for global transcriptional profiling EP Immunolocalization identified changes in mRNA expression that carried over to the protein level Differential expression of non-protein-coding RNAs was AC C confirmed by in situ hybridization A two-way ANOVA of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls Cajal body foci were visualized by COILIN immunolocalization RESULTS: Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly ACCEPTED MANUSCRIPT differentially expressed genes They included molecules known to be expressed by each subpopulation, evidence that the method worked Genes that were differentially expressed between the two groups, in a cell-type specific manner, RI PT encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy complication Gene ontology analysis of the syncytiotrophoblast data SC highlighted the dysregulation of immune functions, morphogenesis, and transport as well as responses to VEGF and progesterone The invasive cytotrophoblast M AN U data provided evidence of alterations in cellular movement, which is consistent with the shallow invasion often associated with severe preeclampsia Other dysregulated pathways included immune, lipid, oxygen and transforming growth factor-beta responses The data for endovascular cytotrophoblasts showed TE D disordered metabolism, signaling and vascular development Additionally, the transcriptional data revealed the differential expression in severe preeclampsia of two classes of non-coding RNAs: lncRNAs and snoRNAs The long non-coding EP RNA, UROTHELIAL CANCER ASSOCIATED 1, was the most highly up regulated in this class In situ hybridization confirmed severe preeclampsia- AC C associated expression in syncytiotrophoblasts The snoRNAs, which chemically modify RNA structure, also correlated with severe preeclampsia Thus, we enumerated Cajal body foci, sites of snoRNA activity, in primary cytotrophoblasts isolated from control and severe preeclampsia placentas In severe preeclampsia, cytotrophoblasts had approximately double the number of these foci as the control samples ACCEPTED MANUSCRIPT CONCLUSION: A laser microdissection approach enabled the identification of novel mRNAs and non-coding RNAs that were misexpressed by various trophoblast subpopulations in severe preeclampsia The results suggested new RI PT avenues of investigation, in particular, the roles of PRG2, Kell blood group determinants and UROTHELIAL CANCER ASSOCIATED in syncytiotrophoblast pathologies Additionally, many of the newly identified SC dysregulated molecules might have clinical utility as biomarkers of severe M AN U preeclampsia KEYWORDS: cytotrophoblasts, laser microdissection, mRNA, non-proteincoding RNA, placenta, potential biomarkers, severe preeclampsia, AC C EP TE D syncytiotrophoblast, transcriptomics ACCEPTED MANUSCRIPT INTRODUCTION In many ways the placenta steers the course of pregnancy Preeclampsia (PE) RI PT is one of the great obstetrical syndromes, which also include intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and placental abruption2 They share the common feature SC of being associated with defects in deep placentation—the depth to which cytotrophoblasts invade the uterus is relatively shallow as compared to normal M AN U pregnancies This is oftentimes accompanied by aberrations in physiologic transformation of the spiral arteries2, How this common denominator diverges into the disparate signs of each condition is not understood PE, which affects 37% of pregnancies in developed countries, is diagnosed according to the maternal signs, which include the new onset of high blood pressure, and variably, TE D proteinuria4 Severe (and early-onset) PE (sPE) entails exacerbation of the hypertension or new findings such as thrombocytopenia, impaired liver function5, PE is also a major cause of premature birth and low birth weight7 Beyond EP pregnancy, development of a pregnancy complication that is associated with AC C faulty placentation, such as PE, positively correlates with an elevated relative risk of maternal cardiovascular disease years later The association between PE and abnormal placentation has been the impetus for studies aimed at understanding the origins and dimensions of the latter defects At a morphological level, abnormalities in formation of the placental bed are thought to be particularly important Cytotrophoblast (CTB) invasion of the C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT uterine wall is variably shallow rather than deep More consistently, CTB remodeling of uterine spiral arteries is incomplete, which has the net effect of reducing maternal blood flow to the placenta9 At a molecular level, CTB RI PT differentiation along the pathway that leads to uterine invasion is abnormal as demonstrated by deficits in the elaborate switching of stage specific antigens that normally enable invasion, vascular mimicry and their cohabitation of the decidua SC with the unusual maternal immune cells that reside in this location10 In addition to morphological and targeted molecular analyses, investigators are also M AN U applying global transcriptional profiling approaches to better understand the placental defects that are associated with PE To date, these studies have focused on chorionic villi (e.g., 11, 12), the maternal-fetal interface (e.g.,13) or purified CTBs as they differentiate along the invasive pathway in vitro (e.g., 14) TE D These studies have the advantage of being unbiased, therefore, enabling the de novo discovery of misregulated genes EP However, the global transcriptional profiling approaches applied to date all have certain disadvantages In tissue-based analyses, signals from the cell type(s) of AC C interest are diluted by the many other cell types that contribute to the gene expression signature of the sample Cultured CTBs, while a more homogenous cell type, may not wholly recapitulate differentiation along the invasive pathway in the absence of maternal cells and the signals they provide To circumvent these problems we applied a laser microdissection approach to placentas from sPE pregnancies This enabled the enrichment and transcriptional profiling of specific TB subpopulations—syncytiotrophoblasts (STBs), invasive CTBs (iCTBs) and Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT endovascular CTBs (eCTBs) The results revealed novel aspects of gene expression in each of the cell types we examined, which could be useful sPE biomarkers if they appear in maternal blood The data also suggested new RI PT theories about the pathogenesis of sPE, particularly in terms of the placental SC manifestations M AN U Materials and Methods Study Design This was a case-control study with the goal of identifying changes in TB gene expression in sPE as compared to nPTB The American College of Obstetrics and Gynecology (ACOG) criteria were used to identify PE patients 5, 15 These TE D include: 1) the new onset of hypertension measured on two occasions of least h apart—blood pressure ≥ 140 mm Hg (systolic) or 90 mm Hg (diastolic) in a EP woman who was normotensive before 20 wks of pregnancy; 2) the appearance of proteinuria—excretion of ≥ 300 mg in a 24-h period or protein/creatinine ratio AC C greater than or equal to 0.3 mg/dL or dipstick reading of 1+, which is used only if other quantitative methods are not available sPE was also diagnosed using ACOG criteria 5, 15, based on additional signs and symptoms: systolic blood pressure ≥ 160 mm Hg and/or diastolic pressure ≥ 110 mm Hg on two occasions at least four hours apart while the patient is on bed rest; proteinuria of ≥ g in a 24-h period or 3+ on urine dipstick; hemolysis (peripheral blood smear and/or LDH ≥ 480); elevated liver function (SGOT ≥ 64 or SGPT ≥ 80); Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT thrombocytopenia (platelets ≤ 100,000); oliguria (≤ 500 cc in 24 h); creatinine ≥ 1.1 mg/dL or a doubling of the serum creatinine concentration with no known with no prior history of seizure disorders RI PT renal dysfunction/disease; cerebral or visual disturbances and/or convulsions As controls, samples were obtained from women who delivered due to nPTL, SC diagnosed according to the criteria recommended by Herron and colleagues 16, including regular uterine contractions after 20 wks or before 37 wks of gestation, M AN U which are ≤ to apart, and accompanied by one or more of the following: (1) progressive changes in the cervix; (2) cervical dilation ≥ cm and/or (3) cervical effacement ≥ 80 percent Patients with evidence of inflammation were excluded on the basis of the following criteria: maternal fever > 100.4°F, uterine TE D tenderness, fetal tachycardia (fetal heart rate > 160 beats per min) and/or (placental) histological criteria compatible with inflammation 17 18, 19 Women with pre-existing medical conditions such as thyroid insufficiency, chronic EP hypertension or diabetes were excluded from the case and the control groups Other exclusion criteria included premature rupture of membranes and/or fetal AC C anomaly The UCSF Institutional Review Board (Committee on Human Research) approved this study Written informed consent was obtained from all donors A laser microdissection approach was used to isolate STBs, iCTBs and eCTBs Total RNA was purified from each sample type and subjected to microarray analyses, which enabled the identification of misexpressed transcripts An Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT M AN U SC RI PT Name D complement component 1, s subcomponent 3.5 cadherin 11, type 2, OB-cadherin (osteoblast) 3.5 homeobox A11 3.5 CXADR-like membrane protein 3.5 complement component 1, r subcomponent 3.5 chemokine (C motif) ligand 3.5 plasminogen activator, tissue 3.5 polypeptide N-acetylgalactosaminyltransferase 15 3.5 TWIST neighbor 3.5 microsomal glutathione S-transferase 3.5 interferon-induced protein 44 3.5 chemokine (C-C motif) ligand 13 3.4 sulfide quinone reductase-like (yeast) 3.4 toll-like receptor 3.4 matrix metallopeptidase 10 3.4 ATP binding cassette subfamily A member 3.4 killer cell lectin-like receptor subfamily F, member 3.4 prolyl 4-hydroxylase, alpha polypeptide III 3.4 serine carboxypeptidase 3.4 proline rich 15 3.4 eva-1 homolog C (C elegans) 3.3 Kruppel-like factor 3.3 fibromodulin 3.3 neural cell adhesion molecule 3.3 keratocan 3.3 WD repeat domain 72 3.3 T cell receptor gamma joining P1 3.3 WNT1 inducible signaling pathway protein 3.3 killer cell lectin-like receptor subfamily F, member 3.2 T-cell activation RhoGTPase activating protein 3.2 myeloid/lymphoid or mixed-lineage leukemia; translocated to, 11 3.2 potassium channel, voltage gated eag related subfamily H, member 3.2 zinc finger E-box binding homeobox 3.2 single-pass membrane protein with coiled-coil domains 3.2 aldehyde dehydrogenase family, member A2 3.2 major histocompatibility complex, class II, DP alpha 3.2 guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O 3.2 endoplasmic reticulum metallopeptidase 3.2 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3.2 PDZK1 interacting protein 3.2 odd-skipped related transciption factor 3.1 transducer of ERBB2, 3.1 potassium channel, voltage gated Shal related subfamily D, member 3.1 empty spiracles homeobox 3.1 ceramide synthase 3.1 mucin 16, cell surface associated 3.1 glutamate receptor, ionotropic, AMPA 3.1 galactosidase beta like 3.1 C-type lectin domain family 2, member B 3.1 GPRIN family member 3.1 solute carrier family (neuronal/epithelial high affinity glutamate transporter, system Xag),3.1 membe milk fat globule-EGF factor protein 3.0 jun B proto-oncogene 3.0 PDZ and LIM domain 3.0 pregnancy-zone protein 3.0 forkhead box O1 3.0 TE D Symbol C1S CDH11 HOXA11 CLMP C1R XCL2 PLAT GALNT15 TWISTNB MGST1 IFI44 CCL13 SQRDL TLR4 MMP10 ABCA8 KLRF1 P4HA3 SCPEP1 PRR15 EVA1C KLF9 FMOD NCAM1 KERA WDR72 TRGJP1 WISP1 KLRF2 TAGAP MLLT11 KCNH1 ZEB1 SMCO3 ALDH1A2 HLA-DPA1 GNAO1 ERMP1 PFKFB3 PDZK1IP1 OSR2 TOB1 KCND2 EMX2 CERS6 MUC16 GRIA3 GLB1L2 CLEC2B GPRIN3 SLC1A1 MFGE8 JUNB PDLIM1 PZP FOXO1 EP eCTB AC C STB nPTB iCTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT Symbol Name ADAMTS2 ADAM metallopeptidase with thrombospondin type motif LGALS1 lectin, galactoside-binding, soluble, LUM lumican KLHL13 kelch-like family member 13 TSKU tsukushi, small leucine rich proteoglycan CLIC2 chloride intracellular channel TPST1 tyrosylprotein sulfotransferase PLA2R1 phospholipase A2 receptor SYTL4 synaptotagmin-like IL2RG interleukin receptor, gamma DNER delta/notch like EGF repeat containing LOC643733caspase 4, apoptosis-related cysteine peptidase pseudogene WNT4 wingless-type MMTV integration site family, member STAMBPL1STAM binding protein-like ISLR immunoglobulin superfamily containing leucine-rich repeat NNMT nicotinamide N-methyltransferase STMN2 stathmin KCNA4 potassium channel, voltage gated shaker related subfamily A, member VIM vimentin KHDRBS3 KH domain containing, RNA binding, signal transduction associated CXCL5 chemokine (C-X-C motif) ligand SETDB2 SET domain, bifurcated CYBRD1 cytochrome b reductase FAM229B family with sequence similarity 229, member B BICC1 BicC family RNA binding protein MSN moesin MCC mutated in colorectal cancers PLCE1 phospholipase C, epsilon ZFP36L2 ZFP36 ring finger protein-like CNKSR2 connector enhancer of kinase suppressor of Ras RNLS renalase, FAD-dependent amine oxidase NPR2 natriuretic peptide receptor DCN decorin C4B complement component 4B (Chido blood group) LINC00924 long intergenic non-protein coding RNA 924 CACNB2 calcium channel, voltage-dependent, beta subunit NAPSA napsin A aspartic peptidase MIR99AHG mir-99a-let-7c cluster host gene CCL5 chemokine (C-C motif) ligand SAMD9L sterile alpha motif domain containing 9-like SMIM10 small integral membrane protein 10 CCL4 chemokine (C-C motif) ligand NR4A2 nuclear receptor subfamily 4, group A, member LAMA4 laminin, alpha PRSS23 protease, serine, 23 LINC00706 long intergenic non-protein coding RNA 706 PTPRC protein tyrosine phosphatase, receptor type, C CTSW cathepsin W ZMAT1 zinc finger, matrin-type ARL3 ADP-ribosylation factor like GTPase PCDHB16 protocadherin beta 16 TSPAN1 tetraspanin AHNAK2 AHNAK nucleoprotein CORIN corin, serine peptidase CCL3L3 chemokine (C-C motif) ligand 3-like PCDHB2 protocadherin beta EP TE D M AN U SC RI PT eCTB AC C STB nPTB iCTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn D 3.0 3.0 3.0 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.6 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT Symbol Name D NCOA7 nuclear receptor coactivator 2.6 NFE2L1 nuclear factor, erythroid 2-like 2.6 PLXNA4 plexin A4 2.6 RASD1 RAS, dexamethasone-induced 2.6 KANK2 KN motif and ankyrin repeat domains 2.6 CERS6-AS1CERS6 antisense RNA 2.6 FAP fibroblast activation protein alpha 2.6 KIR2DL2 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2.6 LOC101928461 uncharacterized LOC101928461 2.6 GJA1 gap junction protein alpha 2.6 HOXA5 homeobox A5 2.5 LINC00987 long intergenic non-protein coding RNA 987 2.5 DDR2 discoidin domain receptor tyrosine kinase 2.5 C4A complement component 4A (Rodgers blood group) 2.5 MX2 MX dynamin-like GTPase 2.5 NR1D1 nuclear receptor subfamily 1, group D, member 2.5 PCOLCE procollagen C-endopeptidase enhancer 2.5 HSD17B6 hydroxysteroid (17-beta) dehydrogenase 2.5 TNFRSF21 tumor necrosis factor receptor superfamily, member 21 2.5 ADGRD1 adhesion G protein-coupled receptor D1 2.5 MDM1 Mdm1 nuclear protein 2.5 ARL4D ADP-ribosylation factor like GTPase 4D 2.5 CD3E CD3e molecule, epsilon (CD3-TCR complex) 2.5 IRS2 insulin receptor substrate 2.5 MMP8 matrix metallopeptidase 2.5 PPDPF pancreatic progenitor cell differentiation and proliferation factor 2.5 PRF1 perforin (pore forming protein) 2.5 RGCC regulator of cell cycle 2.5 SNAP91 synaptosome associated protein 91kDa 2.5 SMOX spermine oxidase 2.5 LOC100507195 uncharacterized LOC100507195 2.5 RCBTB1 regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein2.5 EHD2 EH domain containing 2.5 DSTNP2 destrin (actin depolymerizing factor) pseudogene 2.4 SNCAIP synuclein alpha interacting protein 2.4 GALNT13 polypeptide N-acetylgalactosaminyltransferase 13 2.4 CES1 carboxylesterase 2.4 C11orf70 chromosome 11 open reading frame 70 2.4 NFKBIZ nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta 2.4 NUPR1 nuclear protein 1, transcriptional regulator 2.4 C1orf186 chromosome open reading frame 186 2.4 ODC1 ornithine decarboxylase 2.4 MIR511 microRNA 511 2.4 DCBLD1 discoidin, CUB and LCCL domain containing 2.4 C8orf48 chromosome open reading frame 48 2.4 TMEM176Atransmembrane protein 176A 2.4 ANPEP alanyl (membrane) aminopeptidase 2.4 ALDOC aldolase C, fructose-bisphosphate 2.4 MAP1LC3Cmicrotubule associated protein light chain gamma 2.4 RAB31 RAB31, member RAS oncogene family 2.4 INE2 inactivation escape (non-protein coding) 2.4 ID4 inhibitor of DNA binding 4, dominant negative helix-loop-helix protein 2.4 SLC18A2 solute carrier family 18 (vesicular monoamine transporter), member 2.4 KREMEN1 kringle containing transmembrane protein 2.3 TSPAN5 tetraspanin 2.3 TWIST2 twist family bHLH transcription factor 2.3 EP TE D M AN U SC RI PT eCTB AC C STB nPTB iCTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT Symbol Name D NIPAL2 NIPA-like domain containing 2.3 ZNF239 zinc finger protein 239 2.3 FYN FYN proto-oncogene, Src family tyrosine kinase 2.3 RAI2 retinoic acid induced 2.3 GPR155 G protein-coupled receptor 155 2.3 BHMT2 betaine homocysteine S-methyltransferase 2.3 LINC00473 long intergenic non-protein coding RNA 473 2.3 RDH10 retinol dehydrogenase 10 (all-trans) 2.3 DYX1C1 dyslexia susceptibility candidate 2.3 PPM1H protein phosphatase, Mg2+/Mn2+ dependent, 1H 2.3 FXYD1 FXYD domain containing ion transport regulator 2.3 SIGLEC14 sialic acid binding Ig-like lectin 14 2.3 SLC24A3 solute carrier family 24 (sodium/potassium/calcium exchanger), member 2.3 NPR1 natriuretic peptide receptor 2.3 PRRX1 paired related homeobox 2.3 PCBD1 pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 2.31 alp MRPL33 mitochondrial ribosomal protein L33 2.3 WDR86-AS1WDR86 antisense RNA 2.2 C4orf48 chromosome open reading frame 48 2.2 SGCB sarcoglycan beta 2.2 KIR2DL3 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2.2 TMX3 thioredoxin-related transmembrane protein 2.2 ACSL1 acyl-CoA synthetase long-chain family member 2.2 NAP1L3 nucleosome assembly protein 1-like 2.2 ZDHHC15 zinc finger, DHHC-type containing 15 2.2 C15orf65 chromosome 15 open reading frame 65 2.2 NEO1 neogenin 2.2 VSIG1 V-set and immunoglobulin domain containing 2.2 HOMER2 homer scaffolding protein 2.2 BRE brain and reproductive organ-expressed (TNFRSF1A modulator) 2.2 DDX24 DEAD (Asp-Glu-Ala-Asp) box helicase 24 2.2 ATP13A3 ATPase type 13A3 2.2 AR androgen receptor 2.2 KCNB1 potassium channel, voltage gated Shab related subfamily B, member 2.2 CELF2 CUGBP, Elav-like family member 2.2 WASF3 WAS protein family, member 2.2 RBKS ribokinase 2.1 CRYAB crystallin alpha B 2.1 CD82 CD82 molecule 2.1 ITGAM integrin, alpha M (complement component receptor subunit) 2.1 ICAM1 intercellular adhesion molecule 2.1 BRINP2 bone morphogenetic protein/retinoic acid inducible neural-specific 2.1 MOXD1 monooxygenase, DBH-like 2.1 ADAMTS8 ADAM metallopeptidase with thrombospondin type motif 2.1 FAM159B family with sequence similarity 159, member B 2.1 MANEA mannosidase, endo-alpha 2.0 AXDND1 axonemal dynein light chain domain containing 2.0 TNXB tenascin XB 2.0 EP TE D M AN U SC RI PT eCTB AC C STB nPTB iCTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT TE D M AN U SC RI PT Name D proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein) 6.4 urothelial cancer associated (non-protein coding) 6.0 FBJ murine osteosarcoma viral oncogene homolog 4.3 follistatin-like (secreted glycoprotein) 3.7 metastasis suppressor 1-like 3.5 FBJ murine osteosarcoma viral oncogene homolog B 3.5 fatty acid binding protein 4, adipocyte 3.5 Kell blood group, metallo-endopeptidase 3.4 fibronectin 3.2 ceruloplasmin (ferroxidase) 3.1 histone demethylase UTY-like 3.1 retinol dehydrogenase 13 (all-trans/9-cis) 3.1 jun B proto-oncogene 3.1 solute carrier organic anion transporter family, member 2A1 2.9 EPS8-like 2.9 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2.8 glutaminyl-peptide cyclotransferase 2.8 metallothionein 1F 2.8 poliovirus receptor-related 2.8 SAM and SH3 domain containing 2.8 metallothionein 1G 2.7 SH3 and PX domains 2A 2.6 long intergenic non-protein coding RNA 1150 2.6 inhibin beta A 2.5 TBC1 domain family, member 3G 2.5 B-cell CLL/lymphoma 2.5 leukocyte receptor cluster (LRC) member 2.5 speedy/RINGO cell cycle regulator family member E2 2.5 5-aminolevulinate synthase 2.4 mig-7 2.4 speedy/RINGO cell cycle regulator family member E8, pseudogene 2.4 speedy/RINGO cell cycle regulator family member E2B 2.4 fms-related tyrosine kinase 2.4 additional sex combs like transcriptional regulator 2.3 BTB (POZ) domain containing 16 2.3 chromosome open reading frame 46 2.3 transmembrane protein 45A 2.3 olfactory receptor, family 6, subfamily W, member pseudogene 2.2 TBC1 domain family, member 3B 2.2 zinc finger and BTB domain containing 2.2 endoglin 2.2 neuronatin 2.2 coiled-coil domain containing 183 2.2 WAS protein family homolog pseudogene 2.2 taste receptor, type 2, member 39 2.2 SH3 domain binding glutamate-rich protein like 2.1 N-myc downstream regulated 2.1 FBXL19 antisense RNA (head to head) 2.1 procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2.1 serine/arginine repetitive matrix 2.1 uncharacterized LOC729737 2.1 insulin like growth factor binding protein 2.1 adenosylmethionine decarboxylase 2.1 mannosidase, alpha, class 1C, member 2.1 sialic acid binding Ig-like lectin 2.1 aquaporin (Colton blood group) 2.1 pleckstrin homology domain containing, family A member 2.0 transcription factor 7-like (T-cell specific, HMG-box) 2.0 microRNA 339 2.0 atrophin 2.0 EP Symbol PRG2 UCA1 FOS FSTL3 MTSS1L FOSB FABP4 KEL FN1 CP DNAPTP3 RDH13 JUNB SLCO2A1 EPS8L1 ST8SIA6 QPCT MT1F PVRL4 SASH1 MT1G SH3PXD2A LINC01150 INHBA TBC1D3G BCL6 LENG8 SPDYE2 ALAS2 MIG7 SPDYE8P SPDYE2B FLT1 ASXL3 BTBD16 C5orf46 TMEM45A OR6W1P TBC1D3B ZBTB4 ENG NNAT CCDC183 WASH7P TAS2R39 SH3BGRL3 NDRG1 FBXL19-AS1 PLOD2 SRRM2 LOC729737 IGFBP3 AMD1 MAN1C1 SIGLEC6 AQP1 PLEKHA6 TCF7L2 MIR339 ATN1 AC C STB sPE nPTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT EP TE D M AN U SC RI PT Symbol Name PRKAR2B protein kinase, cAMP-dependent, regulatory, type II, beta ACPP acid phosphatase, prostate MIR181A1 microRNA 181a-1 DUBR DPPA2 upstream binding RNA LRRTM2 leucine rich repeat transmembrane neuronal LOC101927482uncharacterized LOC101927482 FAM26D family with sequence similarity 26, member D WNK3 WNK lysine deficient protein kinase CLDN1 claudin KIAA0319 KIAA0319 CRHBP corticotropin releasing hormone binding protein AFF2 AF4/FMR2 family, member DLGAP5 discs, large (Drosophila) homolog-associated protein MIR561 microRNA 561 KCTD4 potassium channel tetramerization domain containing RAB39A RAB39A, member RAS oncogene family USP46 ubiquitin specific peptidase 46 P2RY1 purinergic receptor P2Y, G-protein coupled, HIST1H2BC histone cluster 1, H2bc LGR5 leucine-rich repeat containing G protein-coupled receptor CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide OR5AK4P olfactory receptor, family 5, subfamily AK, member pseudogene LDHB lactate dehydrogenase B ITGB8 integrin beta LGALS16 lectin, galactoside-binding, soluble, 16 GCNT4 glucosaminyl (N-acetyl) transferase 4, core ZNF502 zinc finger protein 502 SH3TC2 SH3 domain and tetratricopeptide repeats C14orf37 chromosome 14 open reading frame 37 PKIB protein kinase (cAMP-dependent, catalytic) inhibitor beta MIR20B microRNA 20b CARD18 caspase recruitment domain family, member 18 NIPAL1 NIPA-like domain containing PDE10A phosphodiesterase 10A RANBP17 RAN binding protein 17 FAM188B2 family with sequence similarity 188, member B2 ZNF711 zinc finger protein 711 GEN1 GEN1 Holliday junction flap endonuclease NDC80 NDC80 kinetochore complex component GS1-594A7.3 uncharacterized LOC104798195 FAM171B family with sequence similarity 171, member B LINC01091 long intergenic non-protein coding RNA 1091 LINC01119 long intergenic non-protein coding RNA 1119 RASSF6 Ras association (RalGDS/AF-6) domain family member ZNF117 zinc finger protein 117 MICU3 mitochondrial calcium uptake family, member IL33 interleukin 33 GSTA4 glutathione S-transferase alpha SNORD111 small nucleolar RNA, C/D box 111 ANK3 ankyrin 3, node of Ranvier (ankyrin G) P3H2 prolyl 3-hydroxylase LINC00845 long intergenic non-protein coding RNA 845 SNORD126 small nucleolar RNA, C/D box 126 CSTA cystatin A (stefin A) LOC100128386uncharacterized LOC100128386 OTOGL otogelin-like GH1 growth hormone CLRN1-AS1 CLRN1 antisense RNA OR2F1 olfactory receptor, family 2, subfamily F, member (gene/pseudogene) XDH xanthine dehydrogenase AC C STB sPE nPTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn D -2.0 -2.0 -2.0 -2.0 -2.0 -2.0 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.3 -2.3 -2.3 -2.3 -2.3 -2.3 -2.3 -2.3 -2.3 -2.3 -2.3 -2.3 -2.3 -2.4 -2.4 -2.5 -2.5 -2.5 -2.5 -2.5 -2.6 -2.6 -2.6 -2.6 -2.7 -2.7 -2.7 -2.7 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT EP TE D M AN U SC RI PT Symbol Name CFH complement factor H CLRN1 clarin IDO1 indoleamine 2,3-dioxygenase HIST1H4H histone cluster 1, H4h GNGT1 guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide CCDC54 coiled-coil domain containing 54 LINC00284 long intergenic non-protein coding RNA 284 OMG oligodendrocyte myelin glycoprotein PCDH11Y protocadherin 11 Y-linked LINC00882 long intergenic non-protein coding RNA 882 SLC27A2 solute carrier family 27 (fatty acid transporter), member SLC6A15 solute carrier family (neutral amino acid transporter), member 15 CATSPERB catsper channel auxiliary subunit beta ERVFRD-1 endogenous retrovirus group FRD, member NAALADL2 N-acetylated alpha-linked acidic dipeptidase-like TXLNGY taxilin gamma pseudogene, Y-linked POU6F2-AS2 POU6F2 antisense RNA LINC01483 long intergenic non-protein coding RNA 1483 EIF1AY eukaryotic translation initiation factor 1A, Y-linked MATN3 matrilin HSD17B1 hydroxysteroid (17-beta) dehydrogenase TMPRSS11F transmembrane protease, serine 11F PLAC1 placenta specific FRZB frizzled-related protein NTS neurotensin LOC650226 ankyrin repeat domain 26 pseudogene SCN7A sodium channel, voltage gated, type VII alpha subunit LOC100129345uncharacterized LOC100129345 KMO kynurenine 3-monooxygenase (kynurenine 3-hydroxylase) KL klotho NAALADL2-AS3NAALADL2 antisense RNA TTTY15 testis-specific transcript, Y-linked 15 (non-protein coding) ABCG2 ATP binding cassette subfamily G member (Junior blood group) SERPINI1 serpin peptidase inhibitor, clade I (neuroserpin), member ANKRD20A5P ankyrin repeat domain 20 family, member A5, pseudogene USP9Y ubiquitin specific peptidase 9, Y-linked CPS1 carbamoyl-phosphate synthase GSTA3 glutathione S-transferase alpha CSHL1 chorionic somatomammotropin hormone-like ABCB1 ATP binding cassette subfamily B member AC C STB sPE nPTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn D -2.7 -2.8 -2.8 -2.8 -2.8 -2.9 -2.9 -2.9 -2.9 -3.0 -3.0 -3.0 -3.0 -3.0 -3.1 -3.1 -3.1 -3.1 -3.1 -3.2 -3.3 -3.4 -3.4 -3.4 -3.5 -3.5 -3.7 -3.8 -3.9 -3.9 -4.0 -4.1 -4.1 -4.4 -4.5 -4.6 -4.7 -4.8 -5.3 -7.0 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT iCTB M AN U SC RI PT Name metallothionein 1G small proline-rich protein 2G glycerol kinase pseudogene chemokine (C-X-C motif) ligand keratin 7, type II vitrin cytochrome P450, family 4, subfamily F, polypeptide 62, pseudogene coagulation factor VIII-associated uncharacterized LOC729737 uncharacterized LOC101929504 solute carrier family (neurotransmitter transporter), member uncharacterized LOC729218 heme oxygenase hydroxycarboxylic acid receptor aquaporin uncharacterized LOC648987 zinc finger protein 300 pseudogene (functional) urothelial cancer associated (non-protein coding) AHNAK nucleoprotein peptidyl arginine deiminase, type I ephrin-B2 uncharacterized LOC102724784 G protein-coupled receptor, class C, group 5, member A NYN domain and retroviral integrase containing glutamic-pyruvate transaminase (alanine aminotransferase) pyroglutamyl-peptidase I uncharacterized LOC102546229 metastasis suppressor 1-like SHC (Src homology domain containing) transforming protein vascular endothelial growth factor A troponin I type (skeletal, fast) N-myc downstream regulated lysophosphatidylcholine acyltransferase keratin 14, type I solute carrier family (facilitated glucose transporter), member myozenin porcupine homolog (Drosophila) kinase suppressor of ras proopiomelanocortin ciliary rootlet coiled-coil, rootletin pseudogene ceroid-lipofuscinosis, neuronal nuclear transcription factor Y subunit beta zinc finger protein 266 CD47 molecule glutathione S-transferase alpha DPPA2 upstream binding RNA matrix-remodelling associated small nucleolar RNA, H/ACA box 13 adenylate kinase vaccinia related kinase transmembrane protein 62 FK506 binding protein 14 zinc finger protein 732 collagen, type V, alpha uncharacterized LOC100128988 protein kinase, cAMP-dependent, catalytic, beta dpy-19-like (C elegans) syntrophin, beta (dystrophin-associated protein A1, 59kDa, basic component 2) WD repeat domain 41 polycystic kidney disease (autosomal dominant) TE D Symbol MT1G SPRR2G GK3P CXCL8 KRT7 VIT CYP4F62P F8A1 LOC729737 LOC101929504 SLC6A8 LOC729218 HMOX1 HCAR2 AQP9 LOC648987 ZNF300P1 UCA1 AHNAK2 PADI1 EFNB2 LOC102724784 GPRC5A NYNRIN GPT PGPEP1 LOC102546229 MTSS1L SHC3 VEGFA TNNI2 NDRG1 LPCAT1 KRT14 SLC2A3 MYOZ1 PORCN KSR1 POMC CROCCP2 CLN5 NFYB ZNF266 CD47 GSTA4 DUBR MXRA5 SNORA13 AK3 VRK1 TMEM62 FKBP14 ZNF732 COL5A2 LOC100128988 PRKACB DPY19L3 SNTB2 WDR41 PKD2 EP nPTB AC C sPE Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn D 6.5 5.3 5.1 3.5 3.0 3.0 2.9 2.8 2.7 2.7 2.6 2.5 2.5 2.5 2.5 2.5 2.5 2.4 2.4 2.3 2.2 2.2 2.2 2.2 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.0 2.0 2.0 -2.0 -2.0 -2.0 -2.0 -2.0 -2.0 -2.0 -2.0 -2.0 -2.0 -2.0 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.2 -2.2 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT SC RI PT Name D StAR-related lipid transfer domain containing -2.2 collagen, type XII, alpha -2.2 histone cluster 1, H2bi -2.2 hyaluronan and proteoglycan link protein -2.2 tumor protein p53 inducible nuclear protein -2.2 phosphodiesterase 3B, cGMP-inhibited -2.2 transmembrane protein 55A -2.2 sarcoglycan beta -2.2 chloride intracellular channel -2.2 SAM domain and HD domain -2.2 speedy/RINGO cell cycle regulator family member E3 -2.2 ribosomal protein S4, Y-linked -2.2 NOP2/Sun domain family, member -2.2 long intergenic non-protein coding RNA 845 -2.2 matrix metallopeptidase -2.2 twist family bHLH transcription factor -2.2 family with sequence similarity 105, member A -2.3 guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1-2.3 SEMA6A antisense RNA -2.3 angiopoietin like -2.3 IKAROS family zinc finger -2.3 tRNA-yW synthesizing protein -2.3 RAB27B, member RAS oncogene family -2.3 RPGRIP1-like -2.3 hydroxysteroid (17-beta) dehydrogenase -2.3 baculoviral IAP repeat containing -2.3 phosphatidylinositol-4-phosphate 5-kinase, type I, beta -2.3 acyl-CoA synthetase long-chain family member -2.3 pregnancy specific beta-1-glycoprotein 10, pseudogene -2.4 maternal embryonic leucine zipper kinase -2.4 chromosome open reading frame 36 -2.4 small nucleolar RNA, C/D box 114-17 -2.4 chromodomain protein, Y-like -2.4 heparan sulfate (glucosamine) 3-O-sulfotransferase 3B1 -2.4 PSMD5 antisense RNA (head to head) -2.4 microRNA 520e -2.4 Dab, mitogen-responsive phosphoprotein, homolog (Drosophila) -2.4 ADAM metallopeptidase with thrombospondin type motif -2.4 pregnancy specific beta-1-glycoprotein -2.4 solute carrier family 12 (sodium/potassium/chloride transporter), member -2.5 keratin 23, type I -2.5 phorbol-12-myristate-13-acetate-induced protein -2.5 piwi-like RNA-mediated gene silencing -2.5 ADAM-like, decysin -2.5 solute carrier family 25 (mitochondrial carrier; ornithine transporter) member 15 -2.5 CD36 molecule (thrombospondin receptor) -2.5 ATP binding cassette subfamily G member (Junior blood group) -2.6 pregnancy specific beta-1-glycoprotein -2.6 integrin alpha -2.6 ELOVL fatty acid elongase -2.6 G protein-coupled receptor 171 -2.6 ADP-ribosylation factor like GTPase 13B -2.6 RAB3B, member RAS oncogene family -2.6 endogenous retrovirus group 3, member -2.6 interleukin 18 -2.7 ubiquitin specific peptidase 27, X-linked -2.7 solute carrier family 19 (thiamine transporter), member -2.7 alpha-2-macroglobulin -2.7 Rho-related BTB domain containing -2.7 protein tyrosine phosphatase, receptor type, J -2.7 M AN U Symbol STARD4 COL12A1 HIST1H2BI HAPLN3 TP53INP1 PDE3B TMEM55A SGCB CLIC2 SAMHD1 SPDYE3 RPS4Y1 NSUN3 LINC00845 MMP2 TWIST1 FAM105A GNGT1 SEMA6A-AS1 ANGPTL1 IKZF3 TYW5 RAB27B RPGRIP1L HSD17B1 BIRC3 PIP5K1B ACSL5 PSG10P MELK C4orf36 SNORD114-17 CDYL2 HS3ST3B1 PSMD5-AS1 MIR520E DAB2 ADAMTS3 PSG4 SLC12A2 KRT23 PMAIP1 PIWIL4 ADAMDEC1 SLC25A15 CD36 ABCG2 PSG3 ITGA4 ELOVL2 GPR171 ARL13B RAB3B ERV3-1 IL18 USP27X SLC19A3 A2M RHOBTB1 PTPRJ TE D nPTB AC C sPE EP iCTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT iCTB M AN U SC RI PT Name EGF-like-domain, multiple slit guidance ligand fibroblast growth factor binding protein IQ motif containing GTPase activating protein hydroxysteroid (17-beta) dehydrogenase aryl hydrocarbon receptor transforming growth factor beta receptor II anthrax toxin receptor muscleblind-like splicing regulator pregnancy specific beta-1-glycoprotein eukaryotic translation initiation factor 1A, Y-linked purinergic receptor P2Y, G-protein coupled, 12 tissue factor pathway inhibitor fibrillin SLAM family member endogenous retrovirus group FRD, member uncharacterized LOC101929633 CD200 molecule plexin domain containing ankyrin 3, node of Ranvier (ankyrin G) placenta specific jagged DEP domain containing 1B formyl peptide receptor phospholamban insulin-like (placenta) protein kinase (cAMP-dependent, catalytic) inhibitor beta sestrin mitochondrial calcium uptake family, member adhesion G protein-coupled receptor F5 V-set and immunoglobulin domain containing family with sequence similarity 171, member B dynein assembly factor with WDR repeat domains corticotropin releasing hormone PLCE1 antisense RNA RAB39A, member RAS oncogene family poliovirus receptor-related complement component 3a receptor bone morphogenetic protein lectin, galactoside-binding, soluble, 14 kynurenine 3-monooxygenase (kynurenine 3-hydroxylase) adhesion G protein-coupled receptor G6 polycomb group ring finger zinc finger protein 25 ankyrin repeat domain 20 family, member A5, pseudogene small nucleolar RNA, C/D box 114-12 P antigen family, member (prostate associated) pregnancy specific beta-1-glycoprotein absent in melanoma sushi, von Willebrand factor type A, EGF and pentraxin domain containing complement component membrane-spanning 4-domains, subfamily A, member 4A pyruvate dehydrogenase kinase, isozyme cytochrome P450, family 19, subfamily A, polypeptide coagulation factor V (proaccelerin, labile factor) ubiquitin specific peptidase 9, Y-linked testis-specific transcript, Y-linked 15 (non-protein coding) glycoprotein hormones, alpha polypeptide G protein-coupled receptor 34 pregnancy specific beta-1-glycoprotein TE D Symbol EGFL6 SLIT2 FGFBP1 IQGAP2 HSD17B2 AHR TGFBR2 ANTXR1 MBNL3 PSG8 EIF1AY P2RY12 TFPI2 FBN2 SLAMF6 ERVFRD-1 LOC101929633 CD200 PLXDC2 ANK3 PLAC1 JAG1 DEPDC1B FPR3 PLN INSL4 PKIB SESN3 MICU3 ADGRF5 VSIG4 FAM171B DAW1 CRH PLCE1-AS1 RAB39A PVRL3 C3AR1 BMP5 LGALS14 KMO ADGRG6 PCGF5 ZNF25 ANKRD20A5P SNORD114-12 PAGE4 PSG6 AIM1 SVEP1 C7 MS4A4A PDK4 CYP19A1 F5 USP9Y TTTY15 CGA GPR34 PSG1 EP nPTB AC C sPE Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn D -2.7 -2.8 -2.8 -2.8 -2.8 -2.8 -2.8 -2.8 -2.8 -2.9 -2.9 -2.9 -2.9 -2.9 -3.0 -3.0 -3.1 -3.1 -3.1 -3.1 -3.2 -3.2 -3.2 -3.2 -3.2 -3.3 -3.3 -3.3 -3.3 -3.3 -3.4 -3.4 -3.4 -3.4 -3.4 -3.5 -3.5 -3.5 -3.5 -3.6 -3.6 -3.6 -3.7 -3.7 -3.8 -3.9 -4.3 -4.5 -4.6 -4.6 -4.8 -5.1 -5.6 -5.8 -5.8 -7.3 -7.7 -7.9 -9.0 -9.5 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT iCTB D -10.3 -10.7 -14.2 -16.9 Name lectin, galactoside-binding, soluble, 13 periostin, osteoblast specific factor growth hormone chemokine (C-X-C motif) ligand TE D M AN U SC RI PT Symbol LGALS13 POSTN GH2 CXCL9 EP nPTB AC C sPE Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT TE D M AN U SC RI PT Name D renin 6.0 chitinase 3-like (cartilage glycoprotein-39) 3.7 vault RNA 2-1 3.6 heme oxygenase 2.6 golgin A6 family, member A pseudogene 2.5 kinase insert domain receptor 2.4 proline-rich protein BstNI subfamily 2.1 chromosome 10 open reading frame 10 2.1 lysosomal protein transmembrane 2.0 G protein-coupled receptor, class C, group 5, member B 2.0 chloride intracellular channel -2.0 uncharacterized LOC440173 -2.0 hook microtubule-tethering protein -2.0 cadherin-like and PC-esterase domain containing -2.0 family with sequence similarity 171, member B -2.1 polypeptide N-acetylgalactosaminyltransferase -2.1 hyaluronan and proteoglycan link protein -2.1 killer cell lectin-like receptor subfamily F, member -2.1 serine palmitoyltransferase, long chain base subunit -2.1 chromosome 18 open reading frame 54 -2.1 cholinergic receptor, muscarinic -2.2 keratin 23, type I -2.2 RAB27B, member RAS oncogene family -2.2 long intergenic non-protein coding RNA 882 -2.2 Ras association (RalGDS/AF-6) domain family member -2.2 neuromedin U -2.2 sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6D-2.2 epithelial splicing regulatory protein -2.2 C-type lectin domain family 9, member A -2.2 FAT atypical cadherin -2.2 charged multivesicular body protein 4C -2.3 PLCE1 antisense RNA -2.3 interleukin receptor accessory protein-like -2.3 angiotensin I converting enzyme -2.3 neural cell adhesion molecule -2.3 tissue factor pathway inhibitor -2.4 atypical chemokine receptor -2.4 ADAM-like, decysin -2.5 small nucleolar RNA, C/D box 4B -2.6 ribosomal protein S4, Y-linked -2.6 jagged -2.6 adhesion G protein-coupled receptor F5 -2.7 cytochrome P450, family 19, subfamily A, polypeptide -2.7 uncharacterized LOC101929633 -2.7 small nucleolar RNA, C/D box 114-3 -2.8 very low density lipoprotein receptor -2.8 glypican -2.8 dynein assembly factor with WDR repeat domains -2.8 adhesion G protein-coupled receptor G2 -2.8 adhesion G protein-coupled receptor G6 -3.1 osteoglycin -3.3 ELOVL fatty acid elongase -3.4 fibrinogen alpha chain -3.4 family with sequence similarity 66, member A -3.7 fibrinogen beta chain -4.3 small nucleolar RNA, C/D box 114-14 -4.3 EP Symbol REN CHI3L1 VTRNA2-1 HMOX1 LOC645752 KDR PRB1 C10orf10 LAPTM5 GPRC5B CLIC5 LOC440173 HOOK1 CPED1 FAM171B GALNT3 HAPLN1 KLRF2 SPTLC3 C18orf54 CHRM5 KRT23 RAB27B LINC00882 RASSF6 NMU SEMA6D ESRP1 CLEC9A FAT2 CHMP4C PLCE1-AS1 IL1RAPL2 ACE2 NCAM1 TFPI2 ACKR2 ADAMDEC1 SNORD4B RPS4Y1 JAG1 ADGRF5 CYP19A1 LOC101929633 SNORD114-3 VLDLR GPC3 DAW1 ADGRG2 ADGRG6 OGN ELOVL2 FGA FAM66A FGB SNORD114-14 AC C eCTB sPE nPTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ACCEPTED MANUSCRIPT D -4.5 -4.5 -5.5 -5.9 Name shroom family member pregnancy specific beta-1-glycoprotein glycoprotein hormones, alpha polypeptide small nucleolar RNA, C/D box 41 EP TE D M AN U SC RI PT Symbol SHROOM3 PSG1 CGA SNORD41 AC C eCTB sPE nPTB Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn