{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:51:04Z","timestamp":1791183064587,"version":"4.1.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["HD104495"],"award-info":[{"award-number":["HD104495"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K99\/R00"],"award-info":[{"award-number":["K99\/R00"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["HD107262"],"award-info":[{"award-number":["HD107262"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["HD115834"],"award-info":[{"award-number":["HD115834"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P20GM113117"],"award-info":[{"award-number":["P20GM113117"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["HD020676"],"award-info":[{"award-number":["HD020676"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["HD105734"],"award-info":[{"award-number":["HD105734"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["HD112559"],"award-info":[{"award-number":["HD112559"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001864","name":"Sosland Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001864","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Donald C. Johnson Research Endowment Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>What is the contribution of cyclin-dependent kinase inhibitor 1C (CDKN1C) to the regulation of extravillous trophoblast (EVT) cell differentiation and function?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Cell cycle regulators CDKN1C, cyclin-dependent kinase 7 (CDK7), and cyclin E1 (CCNE1) contribute to the development of a healthy placenta by promoting trophoblast stem (TS) cell differentiation to the invasive EVT cell lineage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Early in gestation, cytotrophoblast cells expand and then differentiate into terminal cell lineages, including EVT cells, which invade into uterine tissue and facilitate redirection of maternal resources to the fetus. Cyclin-dependent kinase inhibitor 1C (CDKN1C) is a cell cycle regulator implicated in placental development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>In this study, we used control versus gene-silenced human trophoblast stem cells to assess mechanisms regulating human TS cell differentiation to the EVT cell lineage. An 8-day EVT cell differentiation protocol was utilized. RNA sequencing data include n\u2009=\u20093 for control EVT cells and n\u2009=\u20093 for gene-silenced cells. Assessment of cell counts, DNA content, qPCR, and migration assays were performed with between n\u2009=\u20093 and n\u2009=\u20096.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>In situ hybridization was used to evaluate CDKN1C, CDK7, and CCNE1 transcript expression in human placental tissue sections. A human trophoblast stem cell model was utilized to assess the contributions of CDKN1C, CDK7, and CCNE1 to EVT cell development. Gene perturbation was achieved through lentiviral delivery of short-hairpin RNAs to XY (CT29) and XX (CT27) human TS cell lines. Characterization of cell models and effects of gene silencing were measured by assessing cell morphology and number, reverse transcriptase-quantitative polymerase chain reaction, western blotting, flow cytometry, and co-immunoprecipitation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>CDKN1C was expressed in EVT cells of the placenta and in EVT cells derived from TS cells. Disruption of CDKN1C in TS cells affected cell proliferation, morphology, DNA content, migration, and transcript profiles. CDKN1C is a known modulator of CDK\u2013CCN complexes. CDK7 and CCNE1 were prominently expressed in EVT cells of the placenta and in EVT cells derived from TS cells. CDKN1C was also shown to physically interact with CDK7 and CCNE1. Loss of CDK7 or CCNE1 impaired EVT cell differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LARGE SCALE DATA<\/jats:title>\n                    <jats:p>RNA-seq datasets are available at the Gene Expression Omnibus database under accession number GSE316875.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>In vitro experiments were used to evaluate contribution of cell cycle regulators to EVT cell development. Therefore, these methods do not completely recapitulate the in vivo cell environment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Collectively, these findings demonstrate the importance CDKN1C in regulating EVT cell differentiation and link its actions, at least in part, to CDK7 and CCNE1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Supported by an NIH F31predoctoral fellowship to RLS (HD104495), an NIH K99\/R00 grants to KMV (HD107262) and AMI (HD115834), P20GM113117 to DKJ, NIH grants (HD020676, HD105734, HD112559), The Sosland Foundation, and the Donald C. Johnson Research Endowment Fund.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCLOSURES<\/jats:title>\n                    <jats:p>No disclosures to report.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deag132","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:16:05Z","timestamp":1785237365000},"page":"1672-1687","source":"Crossref","is-referenced-by-count":0,"title":["Cell cycle regulators contribute to extravillous trophoblast cell differentiation and function"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6294-5294","authenticated-orcid":false,"given":"Regan L","family":"Scott","sequence":"first","affiliation":[{"name":"Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]},{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6810-6475","authenticated-orcid":false,"given":"Ayelen","family":"Moreno-Irusta","sequence":"additional","affiliation":[{"name":"Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]},{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-4158","authenticated-orcid":false,"given":"Kaela M","family":"Varberg","sequence":"additional","affiliation":[{"name":"Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]},{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5367-731X","authenticated-orcid":false,"given":"Marija","family":"Kuna","sequence":"additional","affiliation":[{"name":"Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]},{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-8173","authenticated-orcid":false,"given":"David K","family":"Johnson","sequence":"additional","affiliation":[{"name":"Computational Chemical Biology Core and Molecular Modeling Core, University of Kansas , Lawrence, KS,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1539-5063","authenticated-orcid":false,"given":"Hiroaki","family":"Okae","sequence":"additional","affiliation":[{"name":"Department of Trophoblast Research, Institute of Molecular Embryology and Genetics, Kumamoto University , Kumamoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8094-5167","authenticated-orcid":false,"given":"Takahiro","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine , Sendai,","place":["Japan"]},{"name":"Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University , Sendai,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-1592","authenticated-orcid":false,"given":"Michael J","family":"Soares","sequence":"additional","affiliation":[{"name":"Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]},{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]},{"name":"Department of Obstetrics and Gynecology, University of Kansas Medical Center , Kansas City, KS,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"2026100501521611600_deag132-B1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"2026100501521611600_deag132-B2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/15513810802545350","article-title":"Immunohistochemical expression of P57 in placental vascular proliferative disorders of preterm and term placentas","volume":"28","author":"Allias","year":"2009","journal-title":"Fetal Pediatr Pathol"},{"key":"2026100501521611600_deag132-B3","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S1357-2725(96)00178-1","article-title":"Regulation of CDK\/cyclin complexes during the cell cycle","volume":"29","author":"Arellano","year":"1997","journal-title":"Int J Biochem Cell Biol"},{"key":"2026100501521611600_deag132-B4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-023-05869-0","article-title":"Spatial multiomics map of trophoblast development in early pregnancy","volume":"616","author":"Arutyunyan","year":"2023","journal-title":"Nature"},{"key":"2026100501521611600_deag132-B5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.devcel.2008.01.013","article-title":"CDK inhibitors: cell cycle regulators and beyond","volume":"14","author":"Besson","year":"2008","journal-title":"Dev Cell"},{"key":"2026100501521611600_deag132-B6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ajog.2010.08.009","article-title":"The \u201cGreat Obstetrical Syndromes\u201d are associated with disorders of deep placentation","volume":"204","author":"Brosens","year":"2011","journal-title":"Am J Obstet Gynecol"},{"key":"2026100501521611600_deag132-B7","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.ajog.2019.05.044","article-title":"Placental bed research: I. The placental bed: from spiral arteries remodeling to the great obstetrical syndromes","volume":"221","author":"Brosens","year":"2019","journal-title":"Am J Obstet Gynecol"},{"key":"2026100501521611600_deag132-B8","doi-asserted-by":"crossref","first-page":"20140066","DOI":"10.1098\/rstb.2014.0066","article-title":"The placenta: a multifaceted, transient organ","volume":"370","author":"Burton","year":"2015","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"2026100501521611600_deag132-B9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1747-1028-5-2","article-title":"Distinct and redundant functions of cyclin E1 and cyclin E2 in development and cancer","volume":"5","author":"Caldon","year":"2010","journal-title":"Cell Div"},{"key":"2026100501521611600_deag132-B10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1471-2148-14-10","article-title":"Phylogenetic analysis of CDK and cyclin proteins in premetazoan lineages","volume":"14","author":"Cao","year":"2014","journal-title":"BMC Evol Biol"},{"key":"2026100501521611600_deag132-B11","first-page":"269","article-title":"Differential expression of p57kip2, a maternally imprinted cdk inhibitor, in normal human placenta and gestational trophoblastic disease","volume":"78","author":"Chilosi","year":"1998","journal-title":"Lab Investig J Tech Methods Pathol"},{"key":"2026100501521611600_deag132-B12","doi-asserted-by":"crossref","first-page":"102481","DOI":"10.1016\/j.stemcr.2025.102481","article-title":"Hypoxia and loss of GCM1 expression prevent differentiation and contact inhibition in human trophoblast stem cells","volume":"20","author":"Cinkornpumin","year":"2025","journal-title":"Stem Cell Reports"},{"key":"2026100501521611600_deag132-B13","doi-asserted-by":"crossref","first-page":"584590","DOI":"10.3389\/fcell.2020.584590","article-title":"Functional versatility of the CDK inhibitor p57Kip2","volume":"8","author":"Creff","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2026100501521611600_deag132-B14","doi-asserted-by":"crossref","first-page":"e2221526120","DOI":"10.1073\/pnas.2221526120","article-title":"Single-nuclei RNA sequencing (snRNA-seq) uncovers trophoblast cell types and lineages in the mature bovine placenta","volume":"120","author":"Davenport","year":"2023","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026100501521611600_deag132-B15","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/path.4721","article-title":"p57 Kip2 knock-in mouse reveals CDK-independent contribution in the development of Beckwith-Wiedemann syndrome: CDK-independent contribution of p57 inBeckwith-Wiedemann syndrome","volume":"239","author":"Duquesnes","year":"2016","journal-title":"J Pathol"},{"key":"2026100501521611600_deag132-B16","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1093\/hmg\/11.26.3267","article-title":"The maternally transcribed gene p57KIP2 (CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles","volume":"11","author":"Fisher","year":"2002","journal-title":"Hum Mol Genet"},{"key":"2026100501521611600_deag132-B17","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"2026100501521611600_deag132-B18","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1016\/j.placenta.2009.12.012","article-title":"Review: trophoblast-vascular cell interactions in early pregnancy: how to remodel a vessel","volume":"31","author":"Harris","year":"2010","journal-title":"Placenta"},{"key":"2026100501521611600_deag132-B19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1177\/1933719107309588","article-title":"Vascular remodeling and extracellular matrix breakdown in the uterine spiral arteries during pregnancy","volume":"14","author":"Harris","year":"2007","journal-title":"Reprod Sci"},{"key":"2026100501521611600_deag132-B20","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1091\/mbc.11.3.1037","article-title":"Periodic expression of the cyclin-dependent kinase inhibitor p57 Kip2 in trophoblast giant cells defines a G2-like gap phase of the endocycle. In Solomon MJ, editor","volume":"11","author":"Hattori","year":"2000","journal-title":"Mol Biol Cell"},{"key":"2026100501521611600_deag132-B21","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.cell.2015.06.043","article-title":"The BioPlex network: a systematic exploration of the human interactome","volume":"162","author":"Huttlin","year":"2015","journal-title":"Cell"},{"key":"2026100501521611600_deag132-B22","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.placenta.2020.10.029","article-title":"PlacentaCellEnrich: a tool to characterize gene sets using placenta cell-specific gene enrichment analysis","volume":"103","author":"Jain","year":"2021","journal-title":"Placenta"},{"key":"2026100501521611600_deag132-B23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.102.014977","article-title":"Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia","volume":"69","author":"Kaufmann","year":"2003","journal-title":"Biol Reprod"},{"key":"2026100501521611600_deag132-B24","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1007\/s00018-019-03104-6","article-title":"Human placenta and trophoblast development: key molecular mechanisms and model systems","volume":"76","author":"Kn\u00f6fler","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"2026100501521611600_deag132-B25","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/molehr\/gal116","article-title":"Genome-wide expression profiling of placentas in the p57Kip2 model of pre-eclampsia","volume":"13","author":"Knox","year":"2007","journal-title":"Mol Hum Reprod"},{"key":"2026100501521611600_deag132-B26","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1101\/gad.12.3.370","article-title":"Cdk7 is essential for mitosis and for in vivo Cdk-activating kinase activity","volume":"12","author":"Larochelle","year":"1998","journal-title":"Genes Dev"},{"key":"2026100501521611600_deag132-B27","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.cell.2013.02.016","article-title":"X-inactivation, imprinting, and long noncoding RNAs in health and disease","volume":"152","author":"Lee","year":"2013","journal-title":"Cell"},{"key":"2026100501521611600_deag132-B28","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1101\/gad.9.6.639","article-title":"Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution","volume":"9","author":"Lee","year":"1995","journal-title":"Genes Dev"},{"key":"2026100501521611600_deag132-B29","doi-asserted-by":"crossref","first-page":"W199","DOI":"10.1093\/nar\/gkz401","article-title":"WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2026100501521611600_deag132-B30","doi-asserted-by":"crossref","first-page":"2361278","DOI":"10.1080\/14767058.2024.2361278","article-title":"Single-cell RNA sequencing reveals heterogeneity and differential expression of the maternal\u2013fetal interface during ICP and normal pregnancy","volume":"37","author":"Liu","year":"2024","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2026100501521611600_deag132-B31","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/s41422-018-0066-y","article-title":"Single-cell RNA-seq reveals the diversity of trophoblast subtypes and patterns of differentiation in the human placenta","volume":"28","author":"Liu","year":"2018","journal-title":"Cell Res"},{"key":"2026100501521611600_deag132-B32","doi-asserted-by":"crossref","first-page":"dev200563","DOI":"10.1242\/dev.200563","article-title":"IGF2 interacts with the imprinted gene Cdkn1c to promote terminal differentiation of neural stem cells","volume":"150","author":"Lozano-Ure\u00f1a","year":"2023","journal-title":"Development"},{"key":"2026100501521611600_deag132-B33","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.7150\/jca.25395","article-title":"Covalent CDK7 inhibitor THZ1 inhibits myogenic differentiation","volume":"9","author":"Ma","year":"2018","journal-title":"J Cancer"},{"key":"2026100501521611600_deag132-B34","doi-asserted-by":"crossref","first-page":"9813","DOI":"10.1074\/jbc.M109.091496","article-title":"CDKN1C negatively regulates RNA polymerase II C-terminal domain phosphorylation in an E2F1-dependent manner","volume":"285","author":"Ma","year":"2010","journal-title":"J Biol Chem"},{"key":"2026100501521611600_deag132-B35","doi-asserted-by":"crossref","first-page":"e33337","DOI":"10.7554\/eLife.33337","article-title":"Cellular localization of the cell cycle inhibitor Cdkn1c controls growth arrest of adult skeletal muscle stem cells","volume":"7","author":"Mademtzoglou","year":"2018","journal-title":"eLife"},{"key":"2026100501521611600_deag132-B36","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev-cellbio-100814-125620","article-title":"Placenta: the forgotten organ","volume":"31","author":"Maltepe","year":"2015","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2026100501521611600_deag132-B37","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/gb4184","article-title":"Cyclin-dependent kinases","volume":"15","author":"Malumbres","year":"2014","journal-title":"Genome Biol"},{"key":"2026100501521611600_deag132-B38","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.stem.2011.06.014","article-title":"p57 is required for quiescence and maintenance of adult hematopoietic stem cells","volume":"9","author":"Matsumoto","year":"2011","journal-title":"Cell Stem Cell"},{"key":"2026100501521611600_deag132-B39","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1073\/pnas.93.7.3026","article-title":"Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15","volume":"93","author":"Matsuoka","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026100501521611600_deag132-B40","doi-asserted-by":"crossref","first-page":"702046","DOI":"10.3389\/fcell.2021.702046","article-title":"Transcriptomic drivers of differentiation, maturation, and polyploidy in human extravillous trophoblast","volume":"9","author":"Morey","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2026100501521611600_deag132-B41","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/(SICI)1521-1878(199812)20:12<1020::AID-BIES8>3.0.CO;2-D","article-title":"Cip\/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development","volume":"20","author":"Nakayama","year":"1999","journal-title":"Bioessays"},{"key":"2026100501521611600_deag132-B42","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"},{"key":"2026100501521611600_deag132-B43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ctdb.2016.05.001","article-title":"Regulation of the embryonic cell cycle during mammalian preimplantation development","volume":"120","author":"Palmer","year":"2016","journal-title":"Curr Top Dev Biol"},{"key":"2026100501521611600_deag132-B44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41392-024-02080-z","article-title":"Cyclin-dependent protein kinases and cell cycle regulation in biology and disease","volume":"10","author":"Pellarin","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"2026100501521611600_deag132-B45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1017\/CBO9780511750847.014","volume-title":"Placental Bed Disorders Basic Science and its Translation to Obstetrics","author":"Pijnenborg","year":"2010"},{"key":"2026100501521611600_deag132-B46","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.placenta.2005.12.006","article-title":"The uterine spiral arteries in human pregnancy: facts and controversies","volume":"27","author":"Pijnenborg","year":"2006","journal-title":"Placenta"},{"key":"2026100501521611600_deag132-B47","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1172\/JCI200422991","article-title":"Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface","volume":"114","author":"Red-Horse","year":"2004","journal-title":"J Clin Invest"},{"key":"2026100501521611600_deag132-B48","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.placenta.2009.03.013","article-title":"CDKN1C mutations in HELLP\/preeclamptic mothers of Beckwith\u2013Wiedemann syndrome (BWS) patients","volume":"30","author":"Romanelli","year":"2009","journal-title":"Placenta"},{"key":"2026100501521611600_deag132-B49","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat Methods"},{"key":"2026100501521611600_deag132-B50","doi-asserted-by":"crossref","first-page":"e2210633119","DOI":"10.1073\/pnas.2210633119","article-title":"Conservation at the uterine\u2013placental interface","volume":"119","author":"Scott","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026100501521611600_deag132-B51","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.devcel.2024.01.023","article-title":"Single-cell assessment of primary and stem cell-derived human trophoblast organoids as placenta-modeling platforms","volume":"59","author":"Shannon","year":"2024","journal-title":"Dev Cell"},{"key":"2026100501521611600_deag132-B52","doi-asserted-by":"crossref","first-page":"e2403003121","DOI":"10.1073\/pnas.2403003121","article-title":"NOTUM-mediated WNT silencing drives extravillous trophoblast cell lineage development","volume":"121","author":"Shukla","year":"2024","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026100501521611600_deag132-B53","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1387\/ijdb.140083ms","article-title":"Adaptive mechanisms controlling uterine spiral artery remodeling during the establishment of pregnancy","volume":"58","author":"Soares","year":"2014","journal-title":"Int J Dev Biol"},{"key":"2026100501521611600_deag132-B54","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/biolre\/ioy049","article-title":"Hemochorial placentation: development, function, and adaptations","volume":"99","author":"Soares","year":"2018","journal-title":"Biol Reprod"},{"key":"2026100501521611600_deag132-B55","doi-asserted-by":"crossref","first-page":"90","DOI":"10.12688\/f1000research.15016.1","article-title":"Analysis of CDKN1C in fetal growth restriction and pregnancy loss","volume":"8","author":"Suntharalingham","year":"2019","journal-title":"F1000Res"},{"key":"2026100501521611600_deag132-B56","doi-asserted-by":"crossref","first-page":"eaau4788","DOI":"10.1126\/sciadv.aau4788","article-title":"A single-cell survey of the human first-trimester placenta and decidua","volume":"4","author":"Suryawanshi","year":"2018","journal-title":"Sci Adv"},{"key":"2026100501521611600_deag132-B57","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1093\/molehr\/6.11.1019","article-title":"p57Kip2 regulates the proper development of labyrinthine and spongiotrophoblasts","volume":"6","author":"Takahashi","year":"2000","journal-title":"Mol Hum Reprod"},{"key":"2026100501521611600_deag132-B58","doi-asserted-by":"crossref","first-page":"26606","DOI":"10.1073\/pnas.1916019116","article-title":"Loss of p57KIP2 expression confers resistance to contact inhibition in human androgenetic trophoblast stem cells","volume":"116","author":"Takahashi","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026100501521611600_deag132-B59","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1242\/dmm.007328","article-title":"Fetal overgrowth in the Cdkn1c mouse model of Beckwith-Wiedemann syndrome","volume":"4","author":"Tunster","year":"2011","journal-title":"Dis Model Mech"},{"key":"2026100501521611600_deag132-B60","doi-asserted-by":"crossref","first-page":"dev163428","DOI":"10.1242\/dev.163428","article-title":"Development of the human placenta","volume":"146","author":"Turco","year":"2019","journal-title":"Development"},{"key":"2026100501521611600_deag132-B61","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1101\/gad.1718108","article-title":"Differentiation of trophoblast stem cells into giant cells is triggered by p57\/Kip2 inhibition of CDK1 activity","volume":"22","author":"Ullah","year":"2008","journal-title":"Genes Dev"},{"key":"2026100501521611600_deag132-B62","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.1038\/s41467-023-40424-5","article-title":"Extravillous trophoblast cell lineage development is associated with active remodeling of the chromatin landscape","volume":"14","author":"Varberg","year":"2023","journal-title":"Nat Commun"},{"key":"2026100501521611600_deag132-B63","doi-asserted-by":"crossref","first-page":"e2016517118","DOI":"10.1073\/pnas.2016517118","article-title":"ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development","volume":"118","author":"Varberg","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026100501521611600_deag132-B64","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/s42003-025-08393-1","article-title":"Leveraging chorionic villus biopsies for the derivation of patient-specific trophoblast stem cells","volume":"8","author":"Varberg","year":"2025","journal-title":"Commun Biol"},{"key":"2026100501521611600_deag132-B65","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.placenta.2021.04.012","article-title":"Paradigms for investigating invasive trophoblast cell development and contributions to uterine spiral artery remodeling","volume":"113","author":"Varberg","year":"2021","journal-title":"Placenta"},{"key":"2026100501521611600_deag132-B66","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1080\/19336918.2015.1089376","article-title":"Function and control of human invasive trophoblast subtypes: intrinsic vs. maternal control","volume":"10","author":"Velicky","year":"2016","journal-title":"Cell Adh Migr"},{"key":"2026100501521611600_deag132-B67","doi-asserted-by":"crossref","first-page":"e1007698","DOI":"10.1371\/journal.pgen.1007698","article-title":"Genome amplification and cellular senescence are hallmarks of human placenta development. In Mundlos S, editor","volume":"14","author":"Velicky","year":"2018","journal-title":"PLoS Genet"},{"key":"2026100501521611600_deag132-B68","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41586-018-0698-6","article-title":"Single-cell reconstruction of the early maternal-fetal interface in humans","volume":"563","author":"Vento-Tormo","year":"2018","journal-title":"Nature"},{"key":"2026100501521611600_deag132-B69","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.placenta.2010.03.002","article-title":"Cellular and molecular regulation of spiral artery remodelling: lessons from the cardiovascular field","volume":"31","author":"Whitley","year":"2010","journal-title":"Placenta"},{"key":"2026100501521611600_deag132-B70","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1101\/gad.11.8.973","article-title":"Ablation of the CDK inhibitor p57Kip2 results in increased apoptosis and delayed differentiation during mouse development","volume":"11","author":"Yan","year":"1997","journal-title":"Genes Dev"},{"key":"2026100501521611600_deag132-B71","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/387151a0","article-title":"Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome","volume":"387","author":"Zhang","year":"1997","journal-title":"Nature"},{"key":"2026100501521611600_deag132-B72","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1101\/gad.12.20.3162","article-title":"Cooperation between the Cdk inhibitors p27KIP1 and p57KIP2 in the control of tissue growth and development","volume":"12","author":"Zhang","year":"1998","journal-title":"Genes Dev"},{"key":"2026100501521611600_deag132-B73","first-page":"640","article-title":"Genome multiplication of extravillous trophoblast cells in human placenta in the course of differentiation and invasion into endometrium and myometrium. II. Mechanisms of polyploidization","volume":"46","author":"Zybina","year":"2004","journal-title":"Tsitologiia"},{"key":"2026100501521611600_deag132-B74","first-page":"1058","article-title":"Genome multiplication of extravillous trophoblast cells in human placenta in the course of differentiation and invasion into endometrium and myometrium. I. Dynamics of polyploidization","volume":"44","author":"Zybina","year":"2002","journal-title":"Tsitologiia"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/41\/10\/1672\/70761864\/deag132.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/41\/10\/1672\/70761864\/deag132.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:52:34Z","timestamp":1791179554000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/41\/10\/1672\/8768442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":74,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,8,22]]},"published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deag132","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,8,22]]}}}