{"doi":"10.1101/2024.07.12.603303","title":"A Single Trophoblast Layer Acts as the Gatekeeper at the Endothelial-Hematopoietic Crossroad in the Placenta","abstract":"During embryonic development the placental vasculature acts as a major hematopoietic niche, where endothelial to hematopoietic transition ensures emergence of hematopoietic stem cells (HSCs). However, the molecular mechanisms that regulate the placental hematoendothelial niche are poorly understood. 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491416,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":499679,"name":"Ananya Ghosh","orcid":"0000-0002-7543-1409","position":1,"is_corresponding":false},{"id":870055,"name":"Ram Kumar","orcid":"0000-0002-7860-298X","position":2,"is_corresponding":false},{"id":1337370,"name":"Ram Parikshan Kumar","orcid":null,"position":3,"is_corresponding":false},{"id":500338,"name":"Soma Ray","orcid":null,"position":4,"is_corresponding":false},{"id":284304,"name":"Sumedha Gunewardena","orcid":"0000-0003-2097-135X","position":5,"is_corresponding":false},{"id":870056,"name":"Rajnish Kumar","orcid":"0000-0001-8070-8559","position":6,"is_corresponding":false},{"id":758692,"name":"Purbasa Dasgupta","orcid":"0000-0002-5207-5077","position":8,"is_corresponding":false},{"id":870054,"name":"Namrata Roy","orcid":"0000-0002-1934-508X","position":9,"is_corresponding":false},{"id":870053,"name":"Abhik Saha","orcid":"0000-0002-4184-538X","position":10,"is_corresponding":false},{"id":1171524,"name":"Madhu M. Ouseph","orcid":"0000-0002-3422-1675","position":11,"is_corresponding":false},{"id":316405,"name":"Gustavo Leone","orcid":"0000-0002-7617-7449","position":12,"is_corresponding":false},{"id":499684,"name":"Soumen Paul","orcid":"0000-0002-4752-4800","position":13,"is_corresponding":false},{"id":499677,"name":"Pratik Home","orcid":"0000-0002-3159-1603","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T02:08:45.247225Z","pmid":"39071312","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}