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Here, we identify the Rho GTPase-activating protein Dlc1 as an essential regulator of developmental vasculogenesis, and adult bone marrow vascular niche integrity. Endothelial-specific deletion of\n                    <jats:italic>Dlc1<\/jats:italic>\n                    caused embryonic lethality with severe vascular defects. In adult mice, inducible EC-specific\n                    <jats:italic>Dlc1<\/jats:italic>\n                    deletion disrupted the bone marrow vascular architecture, associated with a significant reduction of multipotent hematopoietic progenitors and myeloid-lineage cells. Single-cell RNA sequencing revealed transcriptional reprogramming of\n                    <jats:italic>Dlc1<\/jats:italic>\n                    -deficient ECs, with the emergence of cell subsets displaying altered transcriptional profiles and disrupted expression of key niche signals, including\n                    <jats:italic>Kitl<\/jats:italic>\n                    ,\n                    <jats:italic>Cxcl12<\/jats:italic>\n                    , and\n                    <jats:italic>Pdgfb<\/jats:italic>\n                    . Ligand-receptor interactome analysis demonstrated impaired EC-to-HSPC communication, and the hematopoietic cells exhibited transcriptional features of metabolic stress and reduced biosynthetic activity. These findings position\n                    <jats:italic>Dlc1<\/jats:italic>\n                    as a central regulator of developmental vasculogenesis, adult vascular architecture in the bone marrow, and EC-derived hematopoietic cell support. This work uncovers a previously unrecognized role for\n                    <jats:italic>Dlc1<\/jats:italic>\n                    in coupling vessel function to hematopoietic cell output, with implications for understanding bone marrow failure syndromes and targeting endothelial dysfunction in hematologic diseases.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-03013-1","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:55:44Z","timestamp":1782395744000},"page":"1708-1720","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of endothelial Dlc1 in embryonic vascular development and adult bone marrow hematopoiesis"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0677-2792","authenticated-orcid":false,"given":"Jing-Xin","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0005-8806","authenticated-orcid":false,"given":"Marian E.","family":"Durkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Ting","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Lake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Livak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Tessarollo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-6233","authenticated-orcid":false,"given":"Michael","family":"Kruhlak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Lowy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-3227","authenticated-orcid":false,"given":"Giovanna","family":"Tosato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"3013_CR1","first-page":"2196","volume":"58","author":"BZ Yuan","year":"1998","unstructured":"Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC. 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All rights, title, and interest to these patents have been assigned to the US Department of Health and Human Services; the government conveys a portion of the royalties it receives to its employee inventors under the Federal Technology\u00a0Transfer Act of 1986 (P.L. 99-502). The other authors declare no conflict of interest to disclose.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"All animal procedures were approved by the Institutional Animal Care and Use Committee of the Center for Cancer Research (CCR, Bethesda, MD), National Cancer Institute (NCI), NIH, and conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals (National Academies Press, 2011) and approved institutional protocols.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}}]}}