Work

The Chromatin Remodeler Chd8 Regulates Hematopoietic Stem and Progenitor Cell Survival and Differentiation During Zebrafish Embryogenesis

Year: 2025

Type: article

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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms262110805

Authors: Abrar Ahmed, Xiaona Wei, Dan Zhong, Rahat Ullah, Wei Li, Lili Jing

Institutions: Shanghai Jiao Tong University, Shanghai University

Language: English

Topic: Hematopoietic Stem Cell Transplantation

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499