Identification of a retinoic acid-dependent haemogenic endothelial progenitor from human pluripotent stem cells.

ABSTRACT: The generation of haematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) is a major goal for regenerative medicine. During embryonic development, HSCs derive from haemogenic endothelium (HE) in a NOTCH- and retinoic acid (RA)-dependent manner. Although a WNT-dependent (WNTd) patterning of nascent hPSC mesoderm specifies clonally multipotent intra-embryonic-like HOXA⁺ definitive HE, this HE is functionally unresponsive to RA. Here we show that WNTd mesoderm, before HE specification, is actually composed of two distinct KDR⁺ CD34^neg populations. CXCR4^negCYP26A1⁺ mesoderm gives rise to HOXA⁺ multilineage definitive HE in an RA-independent manner, whereas CXCR4⁺ ALDH1A2⁺ mesoderm gives r

SUBMITTER: Luff SA 

PROVIDER: S-EPMC9109599 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature