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
-
- Enhancer of Zeste Homolog 2 Protein/metabolism*
- Hematopoietic Stem Cells/metabolism*
- Polycomb Repressive Complex 2/metabolism*
- Lymphocytes/metabolism
- Loss of Function Mutation
- Hematopoiesis
- Zebrafish/metabolism*
- Endothelial Cells/metabolism
- Animals
- Single-Cell Analysis
- Gene Knockdown Techniques
- Zebrafish Proteins/metabolism*
- Mice
- RNA-Seq
- Hemangioblasts/metabolism*
- Embryo, Nonmammalian/metabolism
- PubMed
- 34143974 Full text @ Stem Cell Reports
Citation
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. (2021) Sequential regulation of hemogenic fate and hematopoietic stem and progenitor cell formation from arterial endothelium by Ezh1/2. Stem Cell Reports. 16(7):1718-1734.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping