TY - JOUR T1 - DE-NOVO HEMATOPOIESIS FROM THE FETAL LUNG JF - bioRxiv DO - 10.1101/2022.02.14.480402 SP - 2022.02.14.480402 AU - Anthony K. Yeung AU - Carlos Villacorta-Martin AU - Jonathan Lindstrom-Vautrin AU - Anna C. Belkina AU - Kim Vanuytsel AU - Todd W. Dowrey AU - Alexandra B. Ysasi AU - Vladimir Vrbanac AU - Gustavo Mostoslavsky AU - Alejandro B. Balazs AU - George J. Murphy Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/02/14/2022.02.14.480402.abstract N2 - Hemogenic endothelial cells (HECs) are specialized cells that undergo endothelial to hematopoietic transition (EHT) to give rise to hematopoietic progenitors. Though not defined as a hematopoietic organ, the lung houses many resident hematopoietic cells, aids in platelet biogenesis, and is a reservoir for hematopoietic stem and progenitor cells (HSPCs), but lung HECs have never been described. Using explant cultures of murine and human fetal lungs, we demonstrate that the fetal lung is a source of HECs that have the functional capacity to undergo EHT to produce de-novo HSPCs. Flow cytometric and functional assessment of fetal lung explants showed the production of HSPCs that expressed key EHT and pre-HSPC markers. scRNA-Seq and small molecule modulation demonstrated that fetal lung EHT is reliant on canonical EHT signaling pathways. These findings suggest that functional HECs are present in the fetal lung, thus establishing this location as a potential extramedullary site of de-novo hematopoiesis.Competing Interest StatementThe authors have declared no competing interest. ER -