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U.S.A."],"published-print":{"date-parts":[[2024,2,20]]},"abstract":"<jats:p>The placenta establishes a maternal\u2013fetal exchange interface to transport nutrients and gases between the mother and the fetus. Establishment of this exchange interface relies on the development of multinucleated syncytiotrophoblasts (SynT) from trophoblast progenitors, and defect in SynT development often leads to pregnancy failure and impaired embryonic development. Here, we show that mouse embryos with conditional deletion of transcription factors GATA2 and GATA3 in labyrinth trophoblast progenitors (LaTPs) have underdeveloped placenta and die by ~embryonic day 9.5. Single-cell RNA sequencing analysis revealed excessive accumulation of multipotent LaTPs upon conditional deletion of GATA factors. The GATA factor\u2013deleted multipotent progenitors were unable to differentiate into matured SynTs. We also show that the GATA factor\u2013mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. Loss of either GATA2 or GATA3 in cytotrophoblast-derived human trophoblast stem cells (human TSCs) drastically inhibits SynT differentiation potential. Identification of GATA2 and GATA3 target genes along with comparative bioinformatics analyses revealed that GATA factors directly regulate hundreds of common genes in human TSCs, including genes that are essential for SynT development and implicated in preeclampsia and fetal growth retardation. Thus, our study uncovers a conserved molecular mechanism, in which coordinated function of GATA2 and GATA3 promotes trophoblast progenitor-to-SynT commitment, ensuring establishment of the maternal\u2013fetal exchange interface.<\/jats:p>","DOI":"10.1073\/pnas.2310502121","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T15:05:17Z","timestamp":1707750317000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":24,"title":["The GATA transcriptional program dictates cell fate equilibrium to establish the maternal\u2013fetal exchange interface and fetal development"],"prefix":"10.1073","volume":"121","author":[{"given":"Ananya","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-8559","authenticated-orcid":false,"given":"Rajnish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Institute for Reproduction and Developmental Sciences, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7860-298X","authenticated-orcid":false,"given":"Ram P.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Institute for Reproduction and Developmental Sciences, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soma","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4184-538X","authenticated-orcid":false,"given":"Abhik","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1934-508X","authenticated-orcid":false,"given":"Namrata","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5207-5077","authenticated-orcid":false,"given":"Purbasa","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8586-8172","authenticated-orcid":false,"given":"Courtney","family":"Marsh","sequence":"additional","affiliation":[{"name":"Institute for Reproduction and Developmental Sciences, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-4800","authenticated-orcid":false,"given":"Soumen","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Institute for Reproduction and Developmental Sciences, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,2,12]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35080570"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioy049"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100814-125620"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2635424100"},{"key":"e_1_3_4_5_2","first-page":"17","article-title":"Stem cells in the mammalian blastocyst","volume":"97","author":"Rossant J.","year":"2001","unstructured":"J. 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