The Autism-Related Protein CHD8 Contributes to the Stemness and Differentiation of Mouse Hematopoietic Stem Cells

Chromodomain helicase DNA-binding protein 8 (CHD8) is an ATP-dependent chromatin-remodeling factor that is encoded by the most frequently mutated gene in individuals with autism spectrum disorder. Here we show that CHD8 is expressed at a high level in and maintains the stemness of hematopoietic stem cells (HSCs). Conditional deletion of Chd8 specifically in mouse bone marrow induced cell cycle arrest, apoptosis, and a differentiation block in HSCs in association with up-regulation of the expression of p53 target genes. Colony formation assay and bone marrow transplantation revealed that CHD8 deficiency also compromised the stemness of HSCs. Our results thus suggest that the CHD8-p53 axis plays a key role in regulation of the stemness and differentiation of HSCs.