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Using a parietal trophoblast giant cell (TGC)-specific knockout mouse model and single-cell RNA-sequencing, we show that the paracrine factors secreted by the TGCs are critical in the development of this niche. Disruptions in the TGC-specific paracrine signaling leads to the loss of HSC population and the concomitant expansion of a KDR+\/DLL4+\/PROM1+ hematoendothelial cell-population in the placenta. Combining single- cell transcriptomics and receptor-ligand pair analyses, we also define the parietal TGC- dependent paracrine signaling network and identify Integrin signaling as a fundamental regulator of this process. Our study elucidates novel mechanisms by which non-autonomous signaling from the primary parietal TGCs maintain the delicate placental hematopoietic- angiogenic balance and ensures embryonic and extraembryonic development.<\/jats:p>","DOI":"10.1101\/2024.07.12.603303","type":"posted-content","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T21:30:18Z","timestamp":1721165418000},"source":"Crossref","is-referenced-by-count":1,"title":["A Single Trophoblast Layer Acts as the Gatekeeper at the Endothelial-Hematopoietic Crossroad in the Placenta"],"prefix":"10.64898","author":[{"given":"Pratik","family":"Home","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ananya","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram Parikshan","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soma","family":"Ray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumedha","family":"Gunewardena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajnish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purbasa","family":"Dasgupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namrata","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhik","family":"Saha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhu M.","family":"Ouseph","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo W.","family":"Leone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumen","family":"Paul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024071713251266000_2024.07.12.603303v1.1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.103070cg"},{"key":"2024071713251266000_2024.07.12.603303v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.02.001"},{"key":"2024071713251266000_2024.07.12.603303v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.01.001"},{"key":"2024071713251266000_2024.07.12.603303v1.4","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2009.02.010"},{"key":"2024071713251266000_2024.07.12.603303v1.5","unstructured":"5. 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