A specialized bone marrow microenvironment for fetal haematopoiesis

Yang Liu (), Qi Chen, Hyun-Woo Jeong, Bong Ihn Koh, Emma C. Watson, Cong Xu, Martin Stehling, Bin Zhou and Ralf H. Adams ()
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Yang Liu: University of Münster, Faculty of Medicine
Qi Chen: University of Münster, Faculty of Medicine
Hyun-Woo Jeong: University of Münster, Faculty of Medicine
Bong Ihn Koh: University of Münster, Faculty of Medicine
Emma C. Watson: University of Münster, Faculty of Medicine
Cong Xu: University of Münster, Faculty of Medicine
Martin Stehling: Max Planck Institute for Molecular Biomedicine
Bin Zhou: Chinese Academy of Sciences
Ralf H. Adams: University of Münster, Faculty of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract 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 β-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.

Date: 2022
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DOI: 10.1038/s41467-022-28775-x

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