Retinoic acid and Wnt signaling are key regulators in development of hematopoietic stem cells


In the developmental stage of mouse embryo, hematopoietic stem cells (HSCs) are generated via a series events in the aorta-gonad-mesonephros (AGM): from hemogenic endothelium (HE)/pre-HSCs to hematopoietic progenitors. The process involves multiple signaling pathways, including Notch, Wnt, IL-3, Hedgehog, and BMPs. However, the signaling pathways that regulate early hematopoietic development have not been well defined. In this study, Chanda et al. identified retinoic acid (RA) and Wnt signaling pathways as key mediators of HSC development. The article was published on Cell.


In VE-cadherin expressing endothelial cells, Researchers found the activation of RA signaling markedly promoted development of HSCs from AGM-derived HE ex vivo. While, conditional inhibition of RA signaling led to an impairment of HSC development. By further investigating the mechanism, they found the inactivation of Wnt signaling was required in the early stage of HSC development, which provided the evidence that RA signaling promoted HSC development via down-regulation of Wnt signaling. In addition, the inhibition of Wnt signaling pathway enhanced the development of HSCs, even when RA signaling was inactivated. The findings provide insights into the signaling regulation of HSC early-stage-development, as well as help researchers to improve strategies for generating HSCs in vitro.


Cell. 2013 Sep 26;155(1):215-27.

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