Journal
STEM CELL REPORTS
Volume 10, Issue 3, Pages 675-683Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.01.020
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Funding
- NCI grants [R01CA211336, R01CA218600, R01CA215284]
- UNC Cancer Center Core support grant [P30-CA016086]
- Gabrielle's Angel Foundation
- Concern Foundation
- UNC Cores of FACS, Animal Studies, Sequencing and Bioinformatics
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Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC stemness'' genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of stemness'' gene-expression programs and proper function of adult HSCs.
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