CD32 captures committed haemogenic endothelial cells during human embryonic development
Rebecca Scarfò, Lauren N. Randolph, Monah Abou Alezz, Mahassen El Khoury, Amélie Gersch, Zhong-Yin Li, Stephanie A. Luff, Andrea Tavosanis, Giulia Ferrari Ramondo, Sara Valsoni, Sara Cascione, Emma Didelon, Laura Passerini, Giada Amodio, Chiara Brandas, Anna Villa, Silvia Gregori, Ivan Merelli, Jean‐Noël Freund, Christopher M. Sturgeon, Manuela Tavian, Andrea Ditadi
Abstract
Abstract During embryonic development, blood cells emerge from specialized endothelial cells, named haemogenic endothelial cells (HECs). As HECs are rare and only transiently found in early developing embryos, it remains difficult to distinguish them from endothelial cells. Here we performed transcriptomic analysis of 28- to 32-day human embryos and observed that the expression of Fc receptor CD32 ( FCGR2B ) is highly enriched in the endothelial cell population that contains HECs. Functional analyses using human embryonic and human pluripotent stem cell-derived endothelial cells revealed that robust multilineage haematopoietic potential is harboured within CD32 + endothelial cells and showed that 90% of CD32 + endothelial cells are bona fide HECs. Remarkably, these analyses indicated that HECs progress through different states, culminating in FCGR2B expression, at which point cells are irreversibly committed to a haematopoietic fate. These findings provide a precise method for isolating HECs from human embryos and human pluripotent stem cell cultures, thus allowing the efficient generation of haematopoietic cells in vitro.