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Updated: Apr 27, 2026

Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells
Published on: March 31, 2021
Circulation-independent differentiation pathway from extraembryonic mesoderm toward hematopoietic stem cells via
Yosuke Tanaka1, Veronica Sanchez2, Nozomu Takata3
1Laboratory of Stem Cell Biology, Center for Developmental Biology, RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Haematology, Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Abstract:
A large gap exists in our understanding of the course of differentiation from mesoderm to definitive hematopoietic stem cells (HSCs). Previously, we reported that Runx1(+) cells in embryonic day 7.5 (E7.5) embryos contribute to the hemogenic endothelium in the E10.5 aorta-gonad-mesonephros (AGM) region and HSCs in the adult bone marrow. Here, we show that two Runx1(+) populations subdivided by Gata1 expression exist in E7.5 embryos. The hemogenic endothelium and the HSCs are derived only from the Runx1(+)Gata1(-) population. A subset of this population moves from the extra- to intraembryonic region during E7.5-E8.0, where it contributes to the hemogenic endothelium of the dorsal aorta (DA). Migration occurs before the heartbeat is initiated, and it is independent of circulation. This suggests a developmental trajectory from Runx1(+) cells in the E7.5 extraembryonic region to definitive HSCs via the hemogenic endothelium.
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