A specialized bone marrow microenvironment for fetal haematopoiesis

The colonization of bone marrow by haematopoietic stem and progenitor cells is critical for lifelong blood cell formation. Here the authors report distinct features of fetal bone marrow and show that artery-derived signals promote haematopoietic colonization. In adult mammalian bone marrow (BM), vascular endothelial cells and perivascular reticular cells control the function of haematopoietic stem and progenitor cells (HSPCs). During fetal development, the mechanisms regulating the de novo haematopoietic cell colonization of BM remain largely unknown. Here, we show that fetal and adult BM exhibit fundamental differences in cellular composition and molecular interactions by single cell RNA sequencing. While fetal femur is largely devoid of leptin receptor-expressing cells, arterial endothelial cells (AECs) provide Wnt ligand to control the initial HSPC expansion. Haematopoietic stem cells and c-Kit(+) HSPCs are reduced when Wnt secretion by AECs is genetically blocked. We identify Wnt2 as AEC-derived signal that activates beta-catenin-dependent proliferation of fetal HSPCs. Treatment of HSPCs with Wnt2 promotes their proliferation and improves engraftment after transplantation. Our work reveals a fundamental switch in the cellular organization and molecular regulation of BM niches in the embryonic and adult organism.

Automated summary

The colonization of bone marrow by hematopoietic stem and progenitor cells is critical for blood cell formation throughout life. This study reveals distinct features of fetal bone marrow and identifies artery-derived signals, such as Wnt2, that promote hematopoietic colonization. The findings suggest a fundamental switch in the cellular organization and molecular regulation of bone marrow niches between embryonic and adult organisms, and provide insights into improving transplantation outcomes.