PUBLICATION

A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish

Authors
Xia, J., Kang, Z., Xue, Y., Ding, Y., Gao, S., Zhang, Y., Lv, P., Wang, X., Ma, D., Wang, L., Han, J.J., Liu, F.
ID
ZDB-PUB-210401-3
Date
2021
Source
Proceedings of the National Academy of Sciences of the United States of America   118(14): (Journal)
Registered Authors
Liu, Feng, Ma, Dongyuan, Wang, Lu
Keywords
Gpr182, HSPC expansion, caudal hematopoietic tissue, single-cell RNA-seq, zebrafish
Datasets
GEO:GSE120578, GEO:GSE120581, GEO:GSE120509, GEO:GSE146404, GEO:GSE120503
MeSH Terms
  • Animals
  • Cell Lineage
  • Fetus/metabolism
  • Gene Expression Profiling
  • Hematopoiesis*
  • Hematopoietic Stem Cells/physiology*
  • Humans
  • Liver/metabolism
  • Mice
  • Single-Cell Analysis
  • Stem Cell Niche*
  • Zebrafish
PubMed
33785593 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
During vertebrate embryogenesis, fetal hematopoietic stem and progenitor cells (HSPCs) exhibit expansion and differentiation properties in a supportive hematopoietic niche. To profile the developmental landscape of fetal HSPCs and their local niche, here, using single-cell RNA-sequencing, we deciphered a dynamic atlas covering 28,777 cells and 9 major cell types (23 clusters) of zebrafish caudal hematopoietic tissue (CHT). We characterized four heterogeneous HSPCs with distinct lineage priming and metabolic gene signatures. Furthermore, we investigated the regulatory mechanism of CHT niche components for HSPC development, with a focus on the transcription factors and ligand-receptor networks involved in HSPC expansion. Importantly, we identified an endothelial cell-specific G protein-coupled receptor 182, followed by in vivo and in vitro functional validation of its evolutionally conserved role in supporting HSPC expansion in zebrafish and mice. Finally, comparison between zebrafish CHT and human fetal liver highlighted the conservation and divergence across evolution. These findings enhance our understanding of the regulatory mechanism underlying hematopoietic niche for HSPC expansion in vivo and provide insights into improving protocols for HSPC expansion in vitro.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping