PUBLICATION
The Chromatin Remodeler Chd8 Regulates Hematopoietic Stem and Progenitor Cell Survival and Differentiation During Zebrafish Embryogenesis
- Authors
- Ahmed, A., Wei, X., Zhong, D., Ullah, R., Li, W., Jing, L.
- ID
- ZDB-PUB-251113-21
- Date
- 2025
- Source
- International Journal of Molecular Sciences 26: (Journal)
- Registered Authors
- Keywords
- Brd4, chromodomain helicase DNA-binding protein 8 (CHD8), hematopoietic stem and progenitor cells (HSPCs), p53, zebrafish
- MeSH Terms
-
- Animals
- Apoptosis
- Cell Differentiation*/genetics
- Cell Survival
- Chromatin Assembly and Disassembly
- DNA-Binding Proteins*/genetics
- DNA-Binding Proteins*/metabolism
- Embryonic Development*/genetics
- Gene Expression Regulation, Developmental
- Hematopoiesis
- Hematopoietic Stem Cells*/cytology
- Hematopoietic Stem Cells*/metabolism
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41226840 Full text @ Int. J. Mol. Sci.
Citation
Ahmed, A., Wei, X., Zhong, D., Ullah, R., Li, W., Jing, L. (2025) The Chromatin Remodeler Chd8 Regulates Hematopoietic Stem and Progenitor Cell Survival and Differentiation During Zebrafish Embryogenesis. International Journal of Molecular Sciences. 26:.
Abstract
Chromodomain helicase DNA-binding protein 8 (CHD8), a frequently mutated gene in autism spectrum disorder (ASD), is an ATP-dependent chromatin remodeler with emerging roles in hematopoiesis. While CHD8 is known to maintain hematopoietic stem and progenitor cells (HSPCs) in the bone marrow, its function during developmental hematopoiesis remains undefined. Here, using a zebrafish model, we demonstrate that chd8 loss severely depletes the HSPC pool in the caudal hematopoietic tissue through a p53-dependent apoptotic mechanism. Furthermore, chd8-/- embryos exhibit a p53-independent expansion of myelopoiesis. chd8 deficiency upregulates brd4, which promotes systemic inflammatory cytokine expression. Inhibiting brd4 alleviates cytokine expression, suppresses excessive myelopoiesis, and restores HSPC development. Our findings reveal a dual regulatory mechanism in which chd8 governs HSPC development by repressing p53-mediated apoptosis and constraining brd4-driven immune cell differentiation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping