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Appendix 2. Significantly Differentially Regulated Genes in Term Compared with Second Trimester Amniotic Fluid Supernatant

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Appendix 2. Significantly Differentially Regulated Genes in Term Compared With Second Trimester Amniotic Fluid Supernatant Fold Change in term vs second trimester Amniotic Affymetrix Duplicate Fluid Probe ID probes Symbol Entrez Gene Name 1019.9 217059_at D MUC7 mucin 7, secreted 424.5 211735_x_at D SFTPC surfactant protein C 416.2 206835_at STATH statherin 363.4 214387_x_at D SFTPC surfactant protein C 295.5 205982_x_at D SFTPC surfactant protein C 288.7 1553454_at RPTN repetin solute carrier family 34 (sodium 251.3 204124_at SLC34A2 phosphate), member 2 238.9 206786_at HTN3 histatin 3 161.5 220191_at GKN1 gastrokine 1 152.7 223678_s_at D SFTPA2 surfactant protein A2 130.9 207430_s_at D MSMB microseminoprotein, beta- 99.0 214199_at SFTPD surfactant protein D major histocompatibility complex, class II, 96.5 210982_s_at D HLA-DRA DR alpha 96.5 221133_s_at D CLDN18 claudin 18 94.4 238222_at GKN2 gastrokine 2 93.7 1557961_s_at D LOC100127983 uncharacterized LOC100127983 93.1 229584_at LRRK2 leucine-rich repeat kinase 2 HOXD cluster antisense RNA 1 (non- 88.6 242042_s_at D HOXD-AS1 protein coding) 86.0 205569_at LAMP3 lysosomal-associated membrane protein 3 85.4 232698_at BPIFB2 BPI fold containing family B, member 2 84.4 205979_at SCGB2A1 secretoglobin, family 2A, member 1 84.3 230469_at RTKN2 rhotekin 2 82.2 204130_at HSD11B2 hydroxysteroid (11-beta) dehydrogenase 2 81.9 222242_s_at KLK5 kallikrein-related peptidase 5 77.0 237281_at AKAP14 A kinase (PRKA) anchor protein 14 76.7 1553602_at MUCL1 mucin-like 1 76.3 216359_at D MUC7 mucin 7, secreted collagen, type IV, alpha 3 (Goodpasture 72.7 222073_at D COL4A3 antigen) 71.1 206639_x_at HTN1 histatin 1 69.8 223253_at EPDR1 ependymin related protein 1 (zebrafish) major histocompatibility complex, class II, 69.0 208894_at D HLA-DRA DR alpha 67.7 208004_at PROL1 proline rich, lacrimal 1 65.8 226228_at D AQP4 aquaporin 4 65.2 232578_at D CLDN18 claudin 18 63.2 220026_at CLCA4 chloride channel accessory 4 62.6 219949_at LRRC2 leucine rich repeat containing 2 N-terminal EF-hand calcium binding 61.4 233305_at NECAB1 protein 1 57.3 218835_at D SFTPA2 surfactant protein A2 CCAAT/enhancer binding protein (C/EBP), 56.7 213006_at CEBPD delta Hui L, Wick HC, Edlow AG, Cowan JM, Bianchi DJW. Global gene expression analysis of term amniotic fluid cell-free fetal RNA Obstet Gynecol 2013;121. The authors provided this information as a supplement to their article. © Copyright 2013 American College of Obstetricians and Gynecologists. Page 1 of 94 hydroxysteroid (17-beta) dehydrogenase 6 56.5 37512_at D HSD17B6 homolog (mouse) 55.7 239770_at ESYT3 extended synaptotagmin-like protein 3 cyclin-dependent kinase-like 2 (CDC2- 54.2 236331_at D CDKL2 related kinase) collagen, type IV, alpha 3 (Goodpasture 53.4 214641_at D COL4A3 antigen) 51.7 209597_s_at PNMA2 paraneoplastic Ma antigen 2 49.6 210066_s_at D AQP4 aquaporin 4 49.2 38691_s_at D SFTPC surfactant protein C 47.5 211506_s_at D IL8 interleukin 8 46.2 225575_at D LIFR leukemia inhibitory factor receptor alpha 45.7 236646_at C12orf59 chromosome 12 open reading frame 59 45.5 211498_s_at D NKX3-1 NK3 homeobox 1 regulating synaptic membrane exocytosis 44.3 216184_s_at D RIMS1 1 43.8 235514_at ASPRV1 aspartic peptidase, retroviral-like 1 40.2 202859_x_at D IL8 interleukin 8 39.5 231771_at GJB6 gap junction protein, beta 6, 30kDa 39.4 243938_x_at DNAH5 dynein, axonemal, heavy chain 5 pleckstrin homology domain containing, 39.1 243650_at PLEKHH2 family H (with MyTH4 domain) member 2 FXYD domain containing ion transport 39.0 231058_at FXYD4 regulator 4 38.8 231461_at KRT71 keratin 71 38.7 223278_at GJB2 gap junction protein, beta 2, 26kDa Rho guanine nucleotide exchange factor 38.3 222121_at D ARHGEF26 (GEF) 26 37.8 237732_at PRR9 proline rich 9 37.3 222333_at ALS2CL ALS2 C-terminal like 37.2 205778_at D KLK7 kallikrein-related peptidase 7 37.2 213142_x_at D PION pigeon homolog (Drosophila) CD44 (includes 37.0 212063_at D EG:100330801) CD44 molecule (Indian blood group) 36.9 219554_at RHCG Rh family, C glycoprotein HOXD cluster antisense RNA 1 (non- 36.9 228601_at D HOXD-AS1 protein coding) 36.5 219735_s_at D TFCP2L1 transcription factor CP2-like 1 35.5 230493_at SHISA2 shisa homolog 2 (Xenopus laevis) 34.6 213975_s_at D LYZ lysozyme 34.1 1553722_s_at D RNF152 ring finger protein 152 33.9 214240_at GAL galanin prepropeptide c-ros oncogene 1 , receptor tyrosine 33.5 207569_at ROS1 kinase cytochrome P450, family 4, subfamily B, 33.2 210096_at CYP4B1 polypeptide 1 33.2 1556325_at D FILIP1 filamin A interacting protein 1 33.2 226534_at KITLG KIT ligand 33.1 237120_at KRT77 keratin 77 UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 10 33.0 212256_at D GALNT10 (GalNAc-T10) 32.9 236320_at CCDC17 coiled-coil domain containing 17 32.6 214602_at D COL4A4 collagen, type IV, alpha 4 32.4 237466_s_at D HHIP hedgehog interacting protein 32.0 238383_at D C6orf58 chromosome 6 open reading frame 58 Hui L, Wick HC, Edlow AG, Cowan JM, Bianchi DJW. Global gene expression analysis of term amniotic fluid cell-free fetal RNA Obstet Gynecol 2013;121. The authors provided this information as a supplement to their article. © Copyright 2013 American College of Obstetricians and Gynecologists. Page 2 of 94 chitinase 3-like 1 (cartilage glycoprotein- 31.8 209395_at CHI3L1 39) 31.8 209047_at D AQP1 aquaporin 1 (Colton blood group) 31.5 238332_at ANKRD29 ankyrin repeat domain 29 31.2 1552620_at SPRR4 small proline-rich protein 4 hydroxysteroid (17-beta) dehydrogenase 6 30.7 205700_at D HSD17B6 homolog (mouse) 30.6 209706_at D NKX3-1 NK3 homeobox 1 30.4 204846_at D CP ceruloplasmin (ferroxidase) 30.2 210067_at D AQP4 aquaporin 4 30.0 204924_at TLR2 toll-like receptor 2 ventricular zone expressed PH domain 29.8 229759_s_at D VEPH1 homolog 1 (zebrafish) 29.7 210297_s_at D MSMB microseminoprotein, beta- 29.1 1555745_a_at D LYZ lysozyme caspase recruitment domain family, 29.0 224414_s_at CARD6 member 6 28.7 229152_at FDCSP follicular dendritic cell secreted protein myeloid/lymphoid or mixed-lineage 28.7 1565034_s_at D MLL leukemia (trithorax homolog, Drosophila) metallophosphoesterase domain 28.6 215692_s_at D MPPED2 containing 2 28.1 220407_s_at D TGFB2 transforming growth factor, beta 2 27.9 225987_at D STEAP4 STEAP family member 4 27.6 39402_at D IL1B interleukin 1, beta 26.9 1568879_a_at D LAMA3 laminin, alpha 3 26.8 1570515_a_at D FILIP1 filamin A interacting protein 1 regulating synaptic membrane exocytosis 26.8 231986_at D RIMS1 1 26.8 224540_at LACRT lacritin 26.5 215034_s_at D TM4SF1 transmembrane 4 L six family member 1 advanced glycosylation end product- 26.3 210081_at D AGER specific receptor 25.4 216402_at SEC14L4 SEC14-like 4 (S. cerevisiae) 25.3 204754_at D HLF hepatic leukemia factor 25.2 203400_s_at D TF transferrin major histocompatibility complex, class II, 24.9 213831_at D HLA-DQA1 DQ alpha 1 24.5 204755_x_at D HLF hepatic leukemia factor 24.3 207910_at SCGB1D1 secretoglobin, family 1D, member 1 HIP1 (includes 24.2 226364_at D EG:176224) huntingtin interacting protein 1 24.2 212951_at D GPR116 G protein-coupled receptor 116 23.6 223775_at D HHIP hedgehog interacting protein 23.5 207802_at CRISP3 cysteine-rich secretory protein 3 family with sequence similarity 20, 23.3 242945_at D FAM20A member A transglutaminase 3 (E polypeptide, protein-glutamine-gamma- 23.1 206004_at TGM3 glutamyltransferase) solute carrier family 22 (extraneuronal 22.8 205421_at SLC22A3 monoamine transporter), member 3 22.7 214063_s_at D TF transferrin 22.7 218711_s_at D SDPR serum deprivation response 22.5 213611_at AQP5 aquaporin 5 22.4 1558034_s_at D CP ceruloplasmin (ferroxidase) Hui L, Wick HC, Edlow AG, Cowan JM, Bianchi DJW. Global gene expression analysis of term amniotic fluid cell-free fetal RNA Obstet Gynecol 2013;121. The authors provided this information as a supplement to their article. © Copyright 2013 American College of Obstetricians and Gynecologists. Page 3 of 94 ST3 beta-galactoside alpha-2,3- 22.3 210942_s_at ST3GAL6 sialyltransferase 6 erythrocyte membrane protein band 4.1 22.3 225855_at D EPB41L5 like 5 caspase recruitment domain family, 22.2 231733_at CARD18 member 18 22.1 204735_at PDE4A phosphodiesterase 4A, cAMP-specific 1-acylglycerol-3-phosphate O- 21.7 224480_s_at AGPAT9 acyltransferase 9 ATPase, aminophospholipid transporter 21.6 210192_at D ATP8A1 (APLT), class I, type 8A, member 1 21.5 221019_s_at COLEC12 collectin sub-family member 12 21.4 236741_at D WDR72 WD repeat domain 72 21.2 222719_s_at PDGFC platelet derived growth factor C 21.2 205626_s_at D CALB1 calbindin 1, 28kDa Nance-Horan syndrome (congenital 21.1 228933_at NHS cataracts and dental anomalies) CD44 (includes 20.7 204489_s_at D EG:100330801) CD44 molecule (Indian blood group) HOXD cluster antisense RNA 1 (non- 20.6 239182_at D HOXD-AS1 protein coding) potassium inwardly-rectifying channel, 20.5 210403_s_at KCNJ1 subfamily J, member 1 20.5 1558846_at PNLIPRP3 pancreatic lipase-related protein 3 family with sequence similarity 20, 20.5 241981_at D FAM20A member A 20.5 209387_s_at D TM4SF1 transmembrane 4 L six family member 1 20.3 1557136_at ATP13A4 ATPase type 13A4 20.2 207336_at D SOX5 SRY (sex determining region Y)-box 5 20.2 205832_at CPA4 carboxypeptidase A4 20.1 240388_at KRT27 keratin 27 zymogen granule protein 16 homolog B 19.8 228058_at ZG16B (rat) 19.8 213780_at TCHH trichohyalin 19.7 37004_at D SFTPB surfactant protein B 19.6 1555800_at D ZNF385B zinc finger protein 385B ventricular zone expressed PH domain 19.3 234940_s_at D VEPH1 homolog 1 (zebrafish)
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    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
  • CDC2 Mediates Progestin Initiated Endometrial Stromal Cell Proliferation: a PR Signaling to Gene Expression Independently of Its Binding to Chromatin

    CDC2 Mediates Progestin Initiated Endometrial Stromal Cell Proliferation: a PR Signaling to Gene Expression Independently of Its Binding to Chromatin

    CDC2 Mediates Progestin Initiated Endometrial Stromal Cell Proliferation: A PR Signaling to Gene Expression Independently of Its Binding to Chromatin Griselda Vallejo1, Alejandro D. La Greca1., Inti C. Tarifa-Reischle1., Ana C. Mestre-Citrinovitz1, Cecilia Ballare´ 2, Miguel Beato2,3, Patricia Saragu¨ eta1* 1 Instituto de Biologı´a y Medicina Experimental, IByME-Conicet, Buenos Aires, Argentina, 2 Centre de Regulacio´ Geno`mica, (CRG), Barcelona, Spain, 3 University Pompeu Fabra (UPF), Barcelona, Spain Abstract Although non-genomic steroid receptor pathways have been studied over the past decade, little is known about the direct gene expression changes that take place as a consequence of their activation. Progesterone controls proliferation of rat endometrial stromal cells during the peri-implantation phase of pregnancy. We showed that picomolar concentration of progestin R5020 mimics this control in UIII endometrial stromal cells via ERK1-2 and AKT activation mediated by interaction of Progesterone Receptor (PR) with Estrogen Receptor beta (ERb) and without transcriptional activity of endogenous PR and ER. Here we identify early downstream targets of cytoplasmic PR signaling and their possible role in endometrial stromal cell proliferation. Microarray analysis of global gene expression changes in UIII cells treated for 45 min with progestin identified 97 up- and 341 down-regulated genes. The most over-represented molecular functions were transcription factors and regulatory factors associated with cell proliferation and cell cycle, a large fraction of which were repressors down-regulated by hormone. Further analysis verified that progestins regulate Ccnd1, JunD, Usf1, Gfi1, Cyr61, and Cdkn1b through PR- mediated activation of ligand-free ER, ERK1-2 or AKT, in the absence of genomic PR binding.