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| Status |
Public on Jun 17, 2021 |
| Title |
Differential Ezh1/2 regulation of hemogenic fate and hematopoietic stem and progenitor cell formation from arterial endothelium |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Single-cell RNA-sequencing of kdrl:GFP reporter positive FACS sorted cells from EZH1 WT, HET and KO zebrafish 30 hours post-fertilization
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| Contributor(s) |
Najia M, Soto R, North T |
| Citation(s) |
34143974 |
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| Submission date |
May 06, 2021 |
| Last update date |
Jul 27, 2021 |
| Contact name |
Mohamad Ali Najia |
| E-mail(s) |
mohamad.najia@gmail.com
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| Organization name |
Boston Children's Hospital
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| Department |
Hematology/Oncology
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| Lab |
George Daley
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| Street address |
1 Blackfan Circle
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL24995 |
Illumina NovaSeq 6000 (Danio rerio) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA727760 |
| SRA |
SRP318726 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE173972_RAW.tar |
63.9 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
| GSE173972_ezh1_zebrafish_10X_GFP_transcriptome_raw_Seurat.rds.gz |
89.1 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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