期刊
STEM CELL REPORTS
卷 3, 期 3, 页码 502-515出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2014.07.008
关键词
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资金
- NIH
- American Heart Association
- Swedish Brain Foundation (Hjarnfonden)
- David and Astrid Hagelen Foundation
- SSMF (Svenska Sallskapet for Medicinsk Forskning)
- Marie Curie Integration Grant
- Seventh Framework Programme
- European Union
- Swedish Research Council (VR-MH)
- Karolinska Institutet Research Foundations
- Swedish Society of Medicine (SLS)
- Swedish Cancer Society (CF)
- KI Cancer Network
- Swedish Foundation for Strategic Research (SSF)
- Swedish Childhood Cancer Foundation (BCF)
Signaling factors including retinoic acid (RA) and thyroid hormone (T3) promote neuronal, oligodendrocyte, and astrocyte differentiation of cortical neural stem cells (NSCs). However, the functional specificity of transcriptional repressor checkpoints controlling these differentiation programs remains unclear. Here, we show by genome-wide analysis that histone deacetylase (HDAC)2 and HDAC3 show overlapping and distinct promoter occupancy at neuronal and oligodendrocyte-related genes in NSCs. The absence of HDAC3, but not HDAC2, initiated a neuronal differentiation pathway in NSCs. The ablation of the corepressor NCOR or HDAC2, in conjunction with T3 treatment, resulted in increased expression of oligodendrocyte genes, revealing a direct HDAC2-mediated repression of Sox8 and Sox10 expression. Interestingly, Sox10 was required also for maintaining the more differentiated state by repression of stem cell programming factors such as Sox2 and Sox9. Distinct and nonredundant actions of NCORs and HDACs are thus critical for control of lineage progression and differentiation programs in neural progenitors.
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