PUBLICATION
DNA methylation safeguards the generation of hematopoietic stem and progenitor cells by repression of Notch signaling
- Authors
- Li, Y., Tang, C., Liu, F., Zhu, C., Liu, F., Zhu, P., Wang, L.
- ID
- ZDB-PUB-220505-6
- Date
- 2022
- Source
- Development (Cambridge, England) 149(10): (Journal)
- Registered Authors
- Liu, Feng, Wang, Lu
- Keywords
- DNA methylation, Dnmt1, Hematopoietic stem and progenitor cell, Notch signaling, Zebrafish
- Datasets
- GEO:GSE189072
- MeSH Terms
-
- Animals
- DNA Methylation/genetics
- Hemangioblasts*/metabolism
- Hematopoietic Stem Cells/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 35502759 Full text @ Development
Citation
Li, Y., Tang, C., Liu, F., Zhu, C., Liu, F., Zhu, P., Wang, L. (2022) DNA methylation safeguards the generation of hematopoietic stem and progenitor cells by repression of Notch signaling. Development (Cambridge, England). 149(10):.
Abstract
The earliest hematopoietic stem and progenitor cells (HSPCs) are generated from the ventral wall of the dorsal aorta, through endothelial-to-hematopoietic transition (EHT) during vertebrate embryogenesis. Notch signaling is critical for HSPC generation across vertebrates; however, the precise control of Notch during this process remains unclear. In the present study, we used multi-omics approaches together with functional assays to assess global DNA methylome dynamics during the endothelial cells-to-HSPCs transition in zebrafish, and determined that DNA methyltransferase 1 (Dnmt1) is essential for HSPC generation via repression of Notch signaling. Depletion of dnmt1 resulted in decreased DNA methylation levels and impaired HSPC production. Mechanistically, we found that loss of dnmt1 induced hypomethylation of Notch genes and consequently elevated Notch activity in hemogenic endothelial cells, thereby repressing the generation of HSPCs. This finding deepens our understanding of HSPC specification in vivo, which will provide helpful insights for designing new strategies for HSPC generation in vitro.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping