{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:52:49Z","timestamp":1785412369581,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,17]]},"reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["S10OD025120"],"award-info":[{"award-number":["S10OD025120"]}],"id":[{"id":"https:\/\/ror.org\/01jdyfj45","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["P30CA060553"],"award-info":[{"award-number":["P30CA060553"]}]},{"award":["R00HL155845"],"award-info":[{"award-number":["R00HL155845"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K08HL159356"],"award-info":[{"award-number":["K08HL159356"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The pulmonary microvasculature consists of two transcriptionally distinct capillary (CAP) endothelial populations, CAP1 and CAP2 cells, that form the alveolar capillary network. While CAP1 and CAP2 are functionally distinct, the transcriptional mechanisms that specify and maintain these endothelial fates remain poorly understood. The Forkhead transcription factor\n                  <jats:italic>Foxf1<\/jats:italic>\n                  regulates vascular development and is implicated in the neonatal disease alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). However, its role in the specification of pulmonary endothelial subtypes has not been defined. Using single cell ATAC-sequencing and RNA-sequencing of developing mouse lung endothelial cells (ECs), we found that\n                  <jats:italic>Foxf1<\/jats:italic>\n                  is broadly expressed across pulmonary ECs but exhibits preferential chromatin accessibility in CAP2 ECs. Endothelial deletion of\n                  <jats:italic>Foxf1<\/jats:italic>\n                  impaired CAP2 specification and disrupted CAP1 identity, unexpectedly leading to the emergence of a mutant CAP1-like population with a macrovascular transcriptional signature. Adult endothelial deletion of\n                  <jats:italic>Foxf1<\/jats:italic>\n                  similarly resulted in loss of capillary identity, demonstrating that\n                  <jats:italic>Foxf1<\/jats:italic>\n                  is required for capillary fate maintenance. Mutant CAP1 ECs upregulated matrix remodeling genes and exhibited altered communication with neighboring mesenchymal populations, suggesting a potential role in disease development. Consistent with these findings, this mutant CAP1 transcriptional signature was present in human lungs with ACDMPV. This work identifies\n                  <jats:italic>Foxf1<\/jats:italic>\n                  as a key transcriptional regulator for the specification and active maintenance of pulmonary capillary EC fate across the lifespan, and positions capillary identity loss as a driver of vascular remodeling.\n                <\/jats:p>","DOI":"10.64898\/2026.06.16.732674","type":"posted-content","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:25:11Z","timestamp":1781738711000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Foxf1<\/i>\n                  is required for the specification and maintenance of pulmonary capillary identity"],"prefix":"10.64898","author":[{"given":"Yun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cell & Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Ceas","sequence":"additional","affiliation":[{"name":"Department of Cell & Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Arteaga","sequence":"additional","affiliation":[{"name":"Department of Cell & Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Bywaters","sequence":"additional","affiliation":[{"name":"Department of Cell & Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"},{"name":"UT Health Science Center, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya V.","family":"Kalin","sequence":"additional","affiliation":[{"name":"Department of Child Health, Phoenix Children\u2019s Research Institute, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA"},{"name":"Phoenix Children\u2019s Center for Cancer and Blood Disorders, Phoenix Children\u2019s Hospital, Phoenix AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir V.","family":"Kalinichenko","sequence":"additional","affiliation":[{"name":"Department of Child Health, Phoenix Children\u2019s Research Institute, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA"},{"name":"Division of Neonatology, Phoenix Children\u2019s Hospital, University of Arizona College of Medicine \u2013 Phoenix, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7126-0518","authenticated-orcid":false,"given":"Luisa","family":"Morales-Nebreda","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University 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