期刊
SCIENCE
卷 353, 期 6307, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaf1644
关键词
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资金
- Francis Crick Institute
- Cancer Research UK [FC001152]
- UK Medical Research Council [FC001152]
- Wellcome Trust [FC001152]
- Intramural Research Program of the NIH, NCI, Center for Cancer Research
- Israel Science Foundation [ISF 1252/12, 657/12]
- European Research Council [ERC-281781]
- Cancer Research UK
- Versus Arthritis [19256] Funding Source: researchfish
- The Francis Crick Institute [10152, 10002, 10009] Funding Source: researchfish
Tumors comprise functionally diverse subpopulations of cells with distinct proliferative potential. Here, we show that dynamic epigenetic states defined by the linker histone H1.0 determine which cells within a tumor can sustain the long-term cancer growth. Numerous cancer types exhibit high inter-and intratumor heterogeneity of H1.0, with H1.0 levels correlating with tumor differentiation status, patient survival, and, at the single-cell level, cancer stem cell markers. Silencing of H1.0 promotes maintenance of self-renewing cells by inducing derepression of megabase-sized gene domains harboring downstream effectors of oncogenic pathways. Self-renewing epigenetic states are not stable, and reexpression of H1.0 in subsets of tumor cells establishes transcriptional programs that restrict cancer cells' long-term proliferative potential and drive their differentiation. Our results uncover epigenetic determinants of tumor-maintaining cells.
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