한빛사논문
Yang Liu1,2,7,*, Qi Chen1,3,4,7, Hyun-Woo Jeong1,7, Bong Ihn Koh1, Emma C. Watson1, Cong Xu1, Martin Stehling5, Bin Zhou6 & Ralf H. Adams1,*
1Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, University of Münster, Faculty of Medicine, Münster D-48149, Germany. 2School of Medicine, South China University of Technology, University Town Campus, Room 505, Building B2, Guangzhou 510006, China. 3Center for cell lineage and development, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. 4China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou 510530, China. 5Flow Cytometry Unit, Max Planck Institute for Molecular Biomedicine, Münster D-48149, Germany. 6State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, A-2112, Shanghai 200031, China. 7These authors contributed equally: Yang Liu, Qi Chen, Hyun-Woo Jeong.
*Corresponding author.
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.
논문정보
관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기