De-novo hematopoiesis from the fetal lung

Blood Adv. 2023 Sep 20:bloodadvances.2022008347. doi: 10.1182/bloodadvances.2022008347. Online ahead of print.ABSTRACTHemogenic endothelial cells (HECs) are specialized cells that undergo endothelial to hematopoietic transition (EHT) to give rise to the earliest precursors of hematopoietic progenitors that will eventually sustain hematopoiesis throughout the lifetime of an organism. Although HECs are thought to be primarily limited to the aorta gonad mesonephros (AGM) during early development, EHT has been described in various other hematopoietic organs and embryonic vessels. 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). However, lung HECs have never been described. Here we demonstrate that the fetal lung is a potential source of HECs that have the functional capacity to undergo EHT to produce de novo HSPCs and their resultant progeny. Explant cultures of murine and human fetal lungs display adherent endothelial cells transitioning into floating hematopoietic cells accompanied by the gradual loss of an endothelial signature. Flow cytometric and functional assessment of fetal lung explants showed the production of multipotent HSPCs that expressed the EHT and pre-HSPC markers EPCR, CD41, CD43 and CD44. scRNA-Seq and small molecule modulation demonstrated that fetal lung HECs rely on canonical signaling pathways to undergo EHT, in...

Source: Adv Data - September 20, 2023 Category: Epidemiology Authors: Anthony K Yeung Carlos Villacorta-Martin Jonathan Lindstrom-Vautrin Anna C Belkina Kim Vanuytsel Todd W Dowrey Alexandra B Ysasi Pushpinder Bawa Feiya Wang Vladimir Vrbanac Gustavo Mostoslavsky Alejandro Balazs George J Murphy Source Type: research