Retinoic Acid Promotes Endothelial Cell Cycle Early G1 State to Enable Human Hemogenic Endothelial Cell Specification
29 Pages Posted: 11 Mar 2020 Sneak Peek Status: Review CompleteMore...
Development of blood-forming (hemogenic) endothelial cells that give rise to hematopoietic stem and progenitor cells (HSPC) is critical during embryogenesis to generate the embryonic and postnatal hematopoietic system. We previously demonstrated that specification of murine hemogenic endothelial cells is promoted by retinoic acid (RA) signaling and requires downstream endothelial cell cycle control. Whether this mechanism is conserved in human hemogenic endothelial cell specification is unknown. Here, we present a novel protocol to derive endothelial cells, hemogenic endothelial cells and blood cells from human embryonic stem cells. Using this model, we demonstrate that RA and cell cycle control play essential roles in human hemogenic endothelial cell specification. That is, RA promotes endothelial cell cycle arrest to enable RA-induced instructive signals to upregulate hematopoietic gene expression. These novel insights will provide guidance for the ex vivo generation of autologous human HSPC for regenerative medicine applications.
Keywords: Human hemogenic endothelial cell specification, HSPC production, retinoic acid signaling, cell cycle control.
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