PUBLICATION

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

Authors
Li, D., Xue, W., Li, M., Dong, M., Wang, J., Wang, X., Li, X., Chen, K., Zhang, W., Wu, S., Zhang, Y., Gao, L., Chen, Y., Chen, J., Zhou, B.O., Zhou, Y., Yao, X., Li, L., Wu, D., Pan, W.
ID
ZDB-PUB-181127-18
Date
2018
Source
Nature   564(7734): 119-124 (Journal)
Registered Authors
Chen, Kai, Dong, Mei, Li, Lin, Pan, Weijun
Keywords
none
MeSH Terms
  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cellular Microenvironment
  • Endothelial Cells/cytology*
  • Hematopoietic Stem Cells/cytology*
  • Macrophages/metabolism*
  • Stem Cell Niche*
  • Vascular Cell Adhesion Molecule-1/metabolism*
  • Zebrafish*
PubMed
30455424 Full text @ Nature
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes