tailieunhanh - Distinctive epigenomes characterize glioma stem cells and their response to differentiation cues

Glioma stem cells (GSCs) are a subpopulation of stem-like cells that contribute to glioblastoma (GBM) aggressiveness, recurrence, and resistance to radiation and chemotherapy. Therapeutically targeting the GSC population may improve patient survival, but unique vulnerabilities need to be identified. | Zhou et al. Genome Biology 2018 19 43 https s13059-018-1420-6 RESEARCH Open Access Distinctive epigenomes characterize glioma stem cells and their response to differentiation cues Dan Zhou1 Bonnie M. Alver1 Shuang Li1 Ryan A. Hlady1 Joyce J. Thompson1 Mark A. Schroeder2 Jeong-Heon Lee3 4 Jingxin Qiu5 Philip H. Schwartz6 Jann N. Sarkaria2 and Keith D. Robertson1 4 7 8 Abstract Background Glioma stem cells GSCs are a subpopulation of stem-like cells that contribute to glioblastoma GBM aggressiveness recurrence and resistance to radiation and chemotherapy. Therapeutically targeting the GSC population may improve patient survival but unique vulnerabilities need to be identified. Results We isolate GSCs from well-characterized GBM patient-derived xenografts PDX characterize their stemness properties using immunofluorescence staining profile their epigenome including 5mC 5hmC 5fC 5caC and two enhancer marks and define their transcriptome. Fetal brain-derived neural stem progenitor cells are used as a comparison to define potential unique and common molecular features between these different brain-derived cells with stem properties. Our integrative study reveals that abnormal expression of ten-eleven-translocation TET family members correlates with global levels of 5mC and 5fC 5caC and may be responsible for the distinct levels of these marks between glioma and neural stem cells. Heterogenous transcriptome and epigenome signatures among GSCs converge on several genes and pathways including DNA damage response and cell proliferation which are highly correlated with TET expression. Distinct enhancer landscapes are also strongly associated with differential gene regulation between glioma and neural stem cells they exhibit unique co- localization patterns with DNA epigenetic mark switching events. Upon differentiation glioma and neural stem cells exhibit distinct responses with regard to TET expression and DNA mark changes in the genome and GSCs fail to .