PROJECT ID: GSE173972

Data source GEO: GSE173972
Description 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-seq 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.
Key word definitive hematopoiesis; aortic endothelium; in-vivo; emergence; ezh2; gata2
Publication Soto RA, Najia MAT, Hachimi M, Frame JM et al. Sequential regulation of hemogenic fate and hematopoietic stem and progenitor cell formation from arterial endothelium by Ezh1/2. Stem Cell Reports 2021 Jul 13;16(7):1718-1734. PMID: 34143974
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.


Dataset Information

Dataset ID Species Tissue / Organ Experiment type Sample Source dataset ID
1. GSE173972 (WT, ezh1+|+) Danio rerio embryo baseline 1.25dpf, Kdrl-positive embryos GEO: GSM5283739
2. GSE173972 (HET, ezh1+|-) Danio rerio embryo hematopoietic 1.25dpf, Kdrl-positive embryos GEO: GSM5283741
3. GSE173972 (KO, ezh1-|-) Danio rerio embryo hematopoietic 1.25dpf, Kdrl-positive embryos GEO: GSM5283743

Clustering Result

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Erythroid cells ENSDARG00000089475 (hbae1.1) marker DOI:10.1016/j.stemcr.2021.05.014
2 Neuron ENSDARG00000008803 (marcksb) marker DOI:10.1016/j.stemcr.2021.05.014
3 Endothelium ENSDARG00000060263 (pecam1) marker DOI:10.1016/j.stemcr.2021.05.014
4 Epithelial cells ENSDARG00000040534 (epcam) marker DOI:10.1016/j.stemcr.2021.05.014
5 Neutrophils ENSDARG00000019521 (mpx) marker DOI:10.1016/j.stemcr.2021.05.014
6 Neuron ENSDARG00000008803 (marcksb) marker DOI:10.1016/j.stemcr.2021.05.014
7 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1016/j.stemcr.2021.05.014
8 Endothelium ENSDARG00000060263 (pecam1) marker DOI:10.1016/j.stemcr.2021.05.014
9 Neuron ENSDARG00000008803 (marcksb) marker DOI:10.1016/j.stemcr.2021.05.014

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Erythroid cells ENSDARG00000089475 (hbae1.1) marker DOI:10.1016/j.stemcr.2021.05.014
2 Erythroid cells ENSDARG00000089475 (hbae1.1) marker DOI:10.1016/j.stemcr.2021.05.014
3 Endothelium ENSDARG00000060263 (pecam1) marker DOI:10.1016/j.stemcr.2021.05.014
4 Epithelial cells ENSDARG00000040534 (epcam) marker DOI:10.1016/j.stemcr.2021.05.014
5 Neuron ENSDARG00000008803 (marcksb) marker DOI:10.1016/j.stemcr.2021.05.014
6 Neutrophils ENSDARG00000019521 (mpx) marker DOI:10.1016/j.stemcr.2021.05.014
7 Neuron ENSDARG00000008803 (marcksb) marker DOI:10.1016/j.stemcr.2021.05.014
8 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1016/j.stemcr.2021.05.014
9 Cardiovascular ENSDARG00000017821 (gata5) marker DOI:10.1016/j.stemcr.2021.05.014
10 Endothelium ENSDARG00000092170 (apoc1) marker DOI:10.1016/j.stemcr.2021.05.014
11 Epithelial cells ENSDARG00000040534 (epcam) marker DOI:10.1016/j.stemcr.2021.05.014

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Erythroid cells ENSDARG00000089475 (hbae1.1) marker DOI:10.1016/j.stemcr.2021.05.014
2 Neuron ENSDARG00000008803 (marcksb) marker DOI:10.1016/j.stemcr.2021.05.014
3 Endothelium ENSDARG00000060263 (pecam1) marker DOI:10.1016/j.stemcr.2021.05.014
4 Epithelial cells ENSDARG00000040534 (epcam) marker DOI:10.1016/j.stemcr.2021.05.014
5 Endothelium ENSDARG00000060263 (pecam1) marker DOI:10.1016/j.stemcr.2021.05.014
6 Neutrophils ENSDARG00000019521 (mpx) marker DOI:10.1016/j.stemcr.2021.05.014
7 Neuron ENSDARG00000008803 (marcksb) marker DOI:10.1016/j.stemcr.2021.05.014
8 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1016/j.stemcr.2021.05.014
9 Erythroid cells ENSDARG00000089475 (hbae1.1) marker DOI:10.1016/j.stemcr.2021.05.014
10 Epithelial cells ENSDARG00000040534 (epcam) marker DOI:10.1016/j.stemcr.2021.05.014