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Nature. 2018 Dec;564(7734):119-124. doi: 10.1038/s41586-018-0709-7. Epub 2018 Nov 19.

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

Author information

1
Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
2
Key Laboratory of Stem Cell Biology, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), CAS, Shanghai, China.
3
Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
4
Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, CAS, Beijing, China.
5
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, CAS, Shanghai, China.
6
State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, Shanghai, China.
7
Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
8
CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei, China.
9
Department of Pharmacology, Vascular Biology and Therapeutic Program, School of Medicine, Yale University, New Haven, CT, USA.
10
Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China. weijunpan@sibs.ac.cn.
11
Key Laboratory of Stem Cell Biology, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), CAS, Shanghai, China. weijunpan@sibs.ac.cn.

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.

PMID:
30455424
PMCID:
PMC6492262
[Available on 2019-12-01]
DOI:
10.1038/s41586-018-0709-7
[Indexed for MEDLINE]

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