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Hematopoietic stem cells (HSCs) develop from hemogenic endothelial cells (HECs) during mouse embryogenesis. Understanding the signaling molecules required for HSC development is crucial for the in vitro derivation of HSCs. Our previous study showed that HSCs were induced from embryonic HECs, isolated at embryonic day 10.5 (E10.5), in serum-free culture conditions with stem cell factor, thrombopoietin, and an endothelial feeder layer (Morino-Koga S., et al., PNAS, 2024).

 

In this study, a group led by Professor Minetaro Ogawa and Mariko Tsuruda, Saori Morino-Koga (Dept. of Cell Differentiation, IMEG) aimed to elucidate signal requirements for inducing HSCs from earlier-stage HECs. Single-cell RNA sequencing (RNA-seq) analysis detected bone morphogenetic protein (BMP) signaling activation in E9.5 HECs. Adding BMP4 to the culture conditions led to the induction of HSCs from E9.5 HECs. Furthermore, isolating BMP4 receptor-expressing HECs from E9.5 embryos enriched progenitors with HSC-forming ability.

 

This study identified BMP4 as an essential factor promoting the differentiation of early HECs into HSCs, opening up new possibilities for the in vitro derivation of HSCs.

 

Schematic of the findings：Early-stage HECs in the mouse dorsal aorta express the BMP4 receptors. These early-stage HECs are exposed to both BMP4 and signalling molecules produced by vascular endothelial cells that do not express BMP4 receptors, leading to HSC differentiation.