{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T21:05:50Z","timestamp":1782248750213,"version":"3.54.5"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The transcription factor ZBED1 is highly expressed in trophoblast cells, but its functions in the processes of trophoblast and placental biology remain elusive. Here, we characterized the role of ZBED1 in trophoblast cell differentiation using an in vitro BeWo cell model. We demonstrate that ZBED1 is enhanced in its expression early after forskolin-induced differentiation of BeWo cells and regulates many of the genes that are differentially expressed as an effect of forskolin treatment. Specifically, genes encoding markers for the differentiation of cytotrophoblast into syncytiotrophoblast and factors essential for trophoblast cell fusion and invasion were negatively regulated by ZBED1, indicating that ZBED1 might be important for maintaining a steady pool of cytotrophoblast cells. In addition, ZBED1 affected genes involved in the regulation of trophoblast cell survival and apoptosis, in agreement with the observed increase in apoptosis upon knockdown of ZBED1 in forskolin-treated BeWo cells. In addition, genes implicated in the differentiation, recruitment, and function of innate immune cells by the placenta were affected by ZBED1, further suggesting a role for this protein in the regulation of maternal immune tolerance. In conclusion, our study implicates ZBED1 in major biological processes of placental biology.<\/jats:p>","DOI":"10.3390\/genes13010133","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T23:17:07Z","timestamp":1642029427000},"page":"133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["ZBED1 Regulates Genes Important for Multiple Biological Processes of the Placenta"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6140-9366","authenticated-orcid":false,"given":"Simone","family":"Johansen","sequence":"first","affiliation":[{"name":"Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Traynor","sequence":"additional","affiliation":[{"name":"Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malene Laage","family":"Ebstrup","sequence":"additional","affiliation":[{"name":"Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel Green","family":"Terp","sequence":"additional","affiliation":[{"name":"Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina B\u00f8g","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-5135","authenticated-orcid":false,"given":"Henrik J\u00f8rn","family":"Ditzel","sequence":"additional","affiliation":[{"name":"Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"},{"name":"Department of Oncology, Odense University Hospital, 5230 Odense, Denmark"},{"name":"Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0845-1952","authenticated-orcid":false,"given":"Morten Frier","family":"Gjerstorff","sequence":"additional","affiliation":[{"name":"Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"},{"name":"Department of Oncology, Odense University Hospital, 5230 Odense, Denmark"},{"name":"Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22928","DOI":"10.1074\/jbc.M303109200","article-title":"Identification of a Human Homologue of the DREF Transcription Factor with a Potential Role in Regulation of the Histone H1 Gene","volume":"278","author":"Ohshima","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3892\/ol.2020.11997","article-title":"ZBED1\/DREF: A transcription factor that regulates cell proliferation","volume":"20","author":"Jin","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7563","DOI":"10.1074\/jbc.M607180200","article-title":"Human DNA Replication-related Element Binding Factor (hDREF) Self-association via hATC Domain Is Necessary for Its Nuclear Accumulation and DNA Binding","volume":"282","author":"Yamashita","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1128\/MCB.01462-06","article-title":"hDREF Regulates Cell Proliferation and Expression of Ribosomal Protein Genes","volume":"27","author":"Yamashita","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11619","DOI":"10.1074\/jbc.M115.713370","article-title":"Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2\u03b1","volume":"291","author":"Yamashita","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_6","first-page":"4019","article-title":"High expression of ZBED1 affects proliferation and apoptosis in gastric cancer","volume":"11","author":"Jiang","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hansen, S.V., Traynor, S., Ditzel, H.J., and Gjerstorff, M.F. (2018). Human DREF\/ZBED1 is a nuclear protein widely expressed in multiple cell types derived from all three primary germ layers. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205461"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/dvg.22017","article-title":"Drosophila DREF acting via the JNK pathway is required for thorax development","volume":"50","author":"Yoshioka","year":"2012","journal-title":"Genes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1111\/j.1365-2443.2004.00775.x","article-title":"DREF is required for EGFR signalling duringDrosophilawing vein development","volume":"9","author":"Yoshida","year":"2004","journal-title":"Genes Cells"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6020","DOI":"10.1128\/MCB.19.9.6020","article-title":"Targeted Expression of the DNA Binding Domain of DRE-Binding Factor, a Drosophila Transcription Factor, Attenuates DNA Replication of the Salivary Gland and Eye Imaginal Disc","volume":"19","author":"Hirose","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7231","DOI":"10.1128\/MCB.21.21.7231-7242.2001","article-title":"Ectopic Expression of DREF Induces DNA Synthesis, Apoptosis, and Unusual Morphogenesis in the Drosophila Eye Imaginal Disc: Possible Interaction with Polycomb and trithorax Group Proteins","volume":"21","author":"Hirose","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5590","DOI":"10.1128\/MCB.25.13.5590-5598.2005","article-title":"DREF Is Required for Efficient Growth and Cell Cycle Progression in Drosophila Imaginal Discs","volume":"25","author":"Hyun","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.mce.2009.12.015","article-title":"New insights into the regulation of human cytotrophoblast cell differentiation","volume":"323","author":"Handwerger","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1477-7827-5-6","article-title":"Control of human trophoblast function","volume":"5","author":"Lunghi","year":"2007","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.thromres.2004.06.038","article-title":"Growth and function of the normal human placenta","volume":"114","author":"Gude","year":"2004","journal-title":"Thromb. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/35001608","article-title":"Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis","volume":"403","author":"Mi","year":"2000","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jmb.2009.07.025","article-title":"Syncytin-2 Plays an Important Role in the Fusion of Human Trophoblast Cells","volume":"392","author":"Vargas","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"R167","DOI":"10.1530\/REP-16-0031","article-title":"The role of syncytins in human reproduction and reproductive organ cancers","volume":"152","author":"Soygur","year":"2016","journal-title":"Reproduction"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Omata, W., Iv, W.E.A., Vandr\u00e9, D.D., and Robinson, J.M. (2013). Trophoblast Cell Fusion and Differentiation Are Mediated by Both the Protein Kinase C and A Pathways. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081003"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32279","DOI":"10.1074\/jbc.274.45.32279","article-title":"A GCM Motif Protein Is Involved in Placenta-specific Expression of Human Aromatase Gene","volume":"274","author":"Yamada","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S104","DOI":"10.1053\/plac.2002.0929","article-title":"Regulatory Transcription Factors Controlling Function and Differentiation of Human Trophoblast\u2014A Review","volume":"24","author":"Loregger","year":"2003","journal-title":"Placenta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1128\/MCB.00655-15","article-title":"A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCG\u03b2 Expression and Cell Differentiation","volume":"36","author":"Cheong","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/aji.12436","article-title":"Cell Signaling Pathways Involved During Invasion and Syncytialization of Trophoblast Cells","volume":"75","author":"Gupta","year":"2015","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tersigni, C., Meli, F., Neri, C., Iacoangeli, A., Franco, R., Lanzone, A., Scambia, G., and Di Simone, N. (2020). Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134756"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ander, S.E., Diamond, M.S., and Coyne, C.B. (2019). Immune responses at the maternal-fetal interface. Sci. Immunol., 4.","DOI":"10.1126\/sciimmunol.aat6114"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/19336918.2015.1135285","article-title":"Decoding the chemokine network that links leukocytes with decidual cells and the trophoblast during early implantation","volume":"10","author":"Ramhorst","year":"2016","journal-title":"Cell Adhes. Migr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.4049\/jimmunol.1401536","article-title":"The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages","volume":"194","author":"Mehta","year":"2015","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.4049\/jimmunol.1100130","article-title":"Macrophages at the Fetal\u2013Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10","volume":"187","author":"Svensson","year":"2011","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jri.2016.08.008","article-title":"Update of syncytiotrophoblast derived extracellular vesicles in normal pregnancy and preeclampsia","volume":"119","author":"Tannetta","year":"2017","journal-title":"J. Reprod. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.4049\/jimmunol.1301885","article-title":"Exosomes Secreted by Human Placenta Carry Functional Fas Ligand and TRAIL Molecules and Convey Apoptosis in Activated Immune Cells, Suggesting Exosome-Mediated Immune Privilege of the Fetus","volume":"191","author":"Stenqvist","year":"2013","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4049\/jimmunol.0803477","article-title":"Human Placenta Expresses and Secretes NKG2D Ligands via Exosomes that Down-Modulate the Cognate Receptor Expression: Evidence for Immunosuppressive Function","volume":"183","author":"Hedlund","year":"2009","journal-title":"J. Immunol."},{"key":"ref_32","unstructured":"(2021, June 01). Cell Atlas\u2014ZBED1\u2014The Human Protein Atlas. Available online: https:\/\/www.proteinatlas.org\/ENSG00000214717-ZBED1\/cell."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1530\/REP-10-0221","article-title":"The choriocarcinoma cell line BeWo: Syncytial fusion and expression of syncytium-specific proteins","volume":"140","author":"Orendi","year":"2010","journal-title":"Reproduction"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/0014-4827(90)90310-7","article-title":"Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro","volume":"186","author":"Wice","year":"1990","journal-title":"Exp. Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_36","unstructured":"(2021, June 01). iRNA-seq: Computational Method for Genome-Wide Assessment of Acute Transcriptional Regulation from Total RNA-Seq Data, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4381047\/."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1210\/er.2005-0003","article-title":"The Role of Apoptosis in the Regulation of Trophoblast Survival and Differentiation during Pregnancy","volume":"26","author":"Abrahams","year":"2005","journal-title":"Endocr. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4614-8289-5_1","article-title":"Gadd45 in Stress Signaling, Cell Cycle Control, and Apoptosis","volume":"793","author":"Salvador","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.bbrc.2017.07.022","article-title":"RELT family members activate p38 and induce apoptosis by a mechanism distinct from TNFR1","volume":"491","author":"Moua","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1093\/abbs\/gmu048","article-title":"New insights into the roles of CHOP-induced apoptosis in ER stress","volume":"46","author":"Li","year":"2014","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1073\/pnas.1008848108","article-title":"Egr1 mediates p53-independent c-Myc-induced apoptosis via a noncanonical ARF-dependent transcriptional mechanism","volume":"108","author":"Boone","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.fob.2015.02.003","article-title":"Kr\u00fcppel-like factor 4 induces apoptosis and inhibits tumorigenic progression in SK-BR-3 breast cancer cells","volume":"5","author":"Wang","year":"2015","journal-title":"FEBS Open Bio."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fcell.2019.00091","article-title":"TNFR1 and TNFR2 in the Control of the Life and Death Balance of Macrophages","volume":"7","author":"Wajant","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1071\/RD18296","article-title":"Caveolin-1 promotes trophoblast cell invasion through the focal adhesion kinase (FAK) signalling pathway during early human placental development","volume":"31","author":"Dai","year":"2019","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_47","first-page":"765","article-title":"EPO improves the proliferation and inhibits apoptosis of trophoblast and decidual stromal cells through activating STAT-5 and inactivating p38 signal in human early pregnancy","volume":"4","author":"Ji","year":"2011","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.devcel.2011.12.022","article-title":"Trophoblasts Regulate the Placental Hematopoietic Niche through PDGF-B Signaling","volume":"22","author":"Chhabra","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gates, K.C., Goetzmann, L.N., Cantlon, J.D., Jeckel, K.M., and Anthony, R.V. (2017). Effect of proline rich 15-deficiency on trophoblast viability and survival. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0174976"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19077","DOI":"10.1038\/s41598-019-55650-5","article-title":"Peptide hormone ELABELA enhances extravillous trophoblast differentiation, but placenta is not the major source of circulating ELABELA in pregnancy","volume":"9","author":"Georgiadou","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/his.12304","article-title":"Decorin and biglycan immunolocalization in non-villous structures of healthy and pathological human placentas","volume":"64","author":"Borbely","year":"2014","journal-title":"Histopathology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1095\/biolreprod.106.056820","article-title":"Heat Shock Protein 1 and the Mitogen-Activated Protein Kinase 14 Pathway Are Important for Mouse Trophoblast Stem Cell Differentiation","volume":"76","author":"Winger","year":"2007","journal-title":"Biol. Reprod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/mrd.22421","article-title":"Inhibin \u03b1 gene expression in human trophoblasts is regulated by interactions between TFAP2 and cAMP signaling pathways","volume":"81","author":"Depoix","year":"2014","journal-title":"Mol. Reprod. Dev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1242\/dev.092155","article-title":"BMP4-directed trophoblast differentiation of human embryonic stem cells is mediated through a \u0394Np63+ cytotrophoblast stem cell state","volume":"140","author":"Li","year":"2013","journal-title":"Development"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"109092","DOI":"10.1016\/j.biopha.2019.109092","article-title":"Estradiol promotes trophoblast viability and invasion by activating SGK1","volume":"117","author":"He","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lv, B., An, Q., Zeng, Q., Zhang, X., Lu, P., Wang, Y., Zhu, X., Ji, Y., Fan, G., and Xue, Z. (2019). Single-cell RNA sequencing reveals regulatory mechanism for trophoblast cell-fate divergence in human peri-implantation conceptuses. PLoS Biol., 17.","DOI":"10.1101\/567362"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.placenta.2006.03.002","article-title":"Involvement of Sp-1 in the Regulation of the Id-1 Gene during Trophoblast Cell Differentiation","volume":"28","author":"Takeda","year":"2007","journal-title":"Placenta"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Collett, G.P., Linton, E.A., Redman, C.W.G., and Sargent, I.L. (2010). Downregulation of Caveolin-1 Enhances Fusion of Human BeWo Choriocarcinoma Cells. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010529"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1101\/gad.268821.115","article-title":"Elf5-centered transcription factor hub controls trophoblast stem cell self-renewal and differentiation through stoichiometry-sensitive shifts in target gene networks","volume":"29","author":"Latos","year":"2015","journal-title":"Genes Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1053\/plac.2001.0779","article-title":"Characterization of the Expression of the Retinoid-related, Testis-associated Receptor (RTR) in Trophoblasts","volume":"23","author":"Mehta","year":"2002","journal-title":"Placenta"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.4049\/jimmunol.180.4.2367","article-title":"Human trophoblasts recruited T lymphocytes and monocytes into decidua by secretion of chemokine CXCL16 and interaction with CXCR6 in the first-trimester pregnancy","volume":"180","author":"Huang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/s41423-018-0019-x","article-title":"Trophoblast-derived CXCL16 induces M2 macrophage polarization that in turn inactivates NK cells at the maternal\u2013fetal interface","volume":"15","author":"Wang","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1002\/eji.200425223","article-title":"Functional involvement of P-selectin and MAdCAM-1 in the recruitment of ?4?7-integrin-expressing monocyte-like cells to the pregnant mouse uterus","volume":"34","author":"Fernekorn","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"106788","DOI":"10.1016\/j.intimp.2020.106788","article-title":"Trophoblast-derived IL-6 serves as an important factor for normal pregnancy by activating Stat3-mediated M2 macrophages polarization","volume":"90","author":"Ding","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Petitbarat, M., Rahmati, M., S\u00e9razin, V., Dubanchet, S., Morvan, C., Wainer, R., De Mazancourt, P., Chaouat, G., Foidart, J.-M., and Munaut, C. (2011). TWEAK Appears as a Modulator of Endometrial IL-18 Related Cytotoxic Activity of Uterine Natural Killers. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014497"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.3389\/fimmu.2019.01823","article-title":"Implicating the Role of GILZ in Glucocorticoid Modulation of T-Cell Activation","volume":"10","author":"Cannarile","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"873","DOI":"10.4049\/jimmunol.1900171","article-title":"Identification of the E3 Ligase TRIM29 as a Critical Checkpoint Regulator of NK Cell Functions","volume":"203","author":"Dou","year":"2019","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7005","DOI":"10.2147\/OTT.S170385","article-title":"TIM-3, a promising target for cancer immunotherapy","volume":"11","author":"He","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1016\/j.febslet.2005.06.029","article-title":"Stimulation of GCMa and syncytin via cAMP mediated PKA signaling in human trophoblastic cells under normoxic and hypoxic conditions","volume":"579","author":"Knerr","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_70","first-page":"2978","article-title":"HSPB8 promotes cancer cell growth by activating the ERK-CREB pathway and is indicative of a poor prognosis in gastric cancer patients","volume":"39","author":"Shen","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.gene.2003.06.001","article-title":"EID-2, a novel member of the EID family of p300-binding proteins inhibits transactivation by MyoD","volume":"318","author":"Ji","year":"2003","journal-title":"Gene"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3389\/fonc.2020.00046","article-title":"Caveolin-1 Promotes Chemoresistance of Gastric Cancer Cells to Cisplatin by Activating WNT\/\u03b2-Catenin Pathway","volume":"10","author":"Wang","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.placenta.2010.07.011","article-title":"Wnt Signalling in Implantation, Decidualisation and Placental Differentiation\u2014Review","volume":"31","author":"Sonderegger","year":"2010","journal-title":"Placenta"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"180081","DOI":"10.1098\/rsob.180081","article-title":"Exploring the links between cancer and placenta development","volume":"8","author":"Costanzo","year":"2018","journal-title":"Open Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"E138","DOI":"10.1002\/mc.22216","article-title":"Zbed3 contributes to malignant phenotype of lung cancer via regulating \u03b2-catenin and P120-catenin","volume":"54","author":"Fan","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"7743","DOI":"10.1073\/pnas.1509193112","article-title":"Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells","volume":"112","author":"Ali","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.stem.2017.11.004","article-title":"Derivation of Human Trophoblast Stem Cells","volume":"22","author":"Okae","year":"2018","journal-title":"Cell Stem Cell"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/1\/133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:27:29Z","timestamp":1760362049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/1\/133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,12]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["genes13010133"],"URL":"https:\/\/doi.org\/10.3390\/genes13010133","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,12]]}}}