中胚葉から造血幹細胞までの発生過程の解明

A large gap exists in our understanding of the course of differentiation from mesoderm to definitive hematopoietic stem cells (HSCs). The first blood cells appear from mesodermal cells at around embryonic day 7.5 (E7.5) with expression of Runx1. Previously, we reported that a subset of Runx1+ cells in E7.5 embryos contribute to hemogenic endothelium in the E10.5 aorta-gonad-mesonephros (AGM) region and HSCs in the adult bone marrow. Here we show that the Runx1+ population was subdivided by Gata1 expression in E7.5 embryos. The hemogenic endothelium and the HSCs were derived only from the Runx1+Gata1- population. This is consistent with the fact that most of the Runx1+ cells are progenitors for primitive erythrocytes that express Gata1. A subset of Runx1+Gata1- population moves from the extra- to intra-embryonic region during E7.5 to E8.0 where they contributed to the hemogenic endothelium of the dorsal aorta. Migration occurred before heartbeat was initiated, and was independent of circulation. This suggests a developmental trajectory from Runx1+ cells in the E7.5 extraembryonic region to definitive HSCs via hemogenic endothelium.