VCAM-1+ macrophages guide the homing of HSPCs to a vascular niche

Dantong Li, Wenzhi Xue, Mei Li, Mei Dong, Jianwei Wang, Xianda Wang, Xiyue Li, Kai Chen, Wenjuan Zhang, Shuang Wu, Yingqi Zhang, Lei Gao, Yujie Chen, Jianfeng Chen, Bo O. Zhou, Yi Zhou, Xuebiao Yao, Lin Li, Dianqing Wu and Weijun Pan ()
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Dantong Li: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Wenzhi Xue: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Mei Li: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Mei Dong: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Jianwei Wang: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Xianda Wang: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Xiyue Li: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Kai Chen: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Wenjuan Zhang: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Shuang Wu: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Yingqi Zhang: Tongji Hospital, Tongji University School of Medicine
Lei Gao: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)
Yujie Chen: University of Chinese Academy of Sciences, CAS
Jianfeng Chen: CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS
Bo O. Zhou: CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS
Yi Zhou: Harvard Medical School
Xuebiao Yao: University of Science and Technology of China
Lin Li: CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS
Dianqing Wu: Vascular Biology and Therapeutic Program, School of Medicine, Yale University
Weijun Pan: University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS)

Nature, 2018, vol. 564, issue 7734, 119-124

Abstract: Abstract Haematopoietic stem and progenitor cells (HSPCs) give rise to all blood lineages that support the entire lifespan of vertebrates1. After HSPCs emerge from endothelial cells within the developing dorsal aorta, homing allows the nascent cells to anchor in their niches for further expansion and differentiation2–5. Unique niche microenvironments, composed of various blood vessels as units of microcirculation and other niche components such as stromal cells, regulate this process6–9. However, the detailed architecture of the microenvironment and the mechanism for the regulation of HSPC homing remain unclear. Here, using advanced live imaging and a cell-labelling system, we perform high-resolution analyses of the HSPC homing in caudal haematopoietic tissue of zebrafish (equivalent to the fetal liver in mammals), and reveal the role of the vascular architecture in the regulation of HSPC retention. We identify a VCAM-1+ macrophage-like niche cell population that patrols the inner surface of the venous plexus, interacts with HSPCs in an ITGA4-dependent manner, and directs HSPC retention. These cells, named ‘usher cells’, together with caudal venous capillaries and plexus, define retention hotspots within the homing microenvironment. Thus, the study provides insights into the mechanism of HSPC homing and reveals the essential role of a VCAM-1+ macrophage population with patrolling behaviour in HSPC retention.

Keywords: Vascular Niche; Capillary Venules; Whole-mount In Situ Hybridization (WISH); WISH Analysis; Zeiss LSM510 Confocal Microscope (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0709-7

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