PUBLICATION

Sequential regulation of hemogenic fate and hematopoietic stem and progenitor cell formation from arterial endothelium by Ezh1/2

Authors
Soto, R.A., Najia, M.A.T., Hachimi, M., Frame, J.M., Yette, G.A., Lummertz da Rocha, E., Stankunas, K., Daley, G.Q., North, T.E.
ID
ZDB-PUB-210622-27
Date
2021
Source
Stem Cell Reports   16(7): 1718-1734 (Journal)
Registered Authors
Keywords
Ezh1, Ezh2, endothelial-to-hematopoietic transition (EHT), hematopoiesis, hematopoietic stem/progenitor cell (HSPC), hemogenic endothelium (HE), zebrafish
Datasets
GEO:GSE173972
MeSH Terms
  • Animals
  • Embryo, Nonmammalian/metabolism
  • Endothelial Cells/metabolism
  • Enhancer of Zeste Homolog 2 Protein/metabolism*
  • Gene Knockdown Techniques
  • Hemangioblasts/metabolism*
  • Hematopoiesis
  • Hematopoietic Stem Cells/metabolism*
  • Loss of Function Mutation
  • Lymphocytes/metabolism
  • Mice
  • Polycomb Repressive Complex 2/metabolism*
  • RNA-Seq
  • Single-Cell Analysis
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed
34143974 Full text @ Stem Cell Reports
Abstract
Across species, hematopoietic stem and progenitor cells (HSPCs) arise during embryogenesis from a specialized arterial population, termed hemogenic endothelium. Here, we describe a mechanistic role for the epigenetic regulator, Enhancer of zeste homolog-1 (Ezh1), in vertebrate HSPC production via regulation of hemogenic commitment. Loss of ezh1 in zebrafish embryos favored acquisition of hemogenic (gata2b) and HSPC (runx1) fate at the expense of the arterial program (ephrinb2a, dll4). In contrast, ezh1 overexpression blocked hematopoietic progression via maintenance of arterial gene expression. The related Polycomb group subunit, Ezh2, functioned in a non-redundant, sequential manner, whereby inhibition had no impact on arterial identity, but was capable of blocking ezh1-knockdown-associated HSPC expansion. Single-cell RNA sequencing across ezh1 genotypes revealed a dropout of ezh1+/- cells among arterial endothelium associated with positive regulation of gene transcription. Exploitation of Ezh1/2 modulation has potential functional relevance for improving in vitro HSPC differentiation from induced pluripotent stem cell sources.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping