| Title |
Distinctive epigenomes characterize glioma stem cells and their response to differentiation cues
|
|---|---|
| Published in |
Genome Biology, March 2018
|
| DOI | 10.1186/s13059-018-1420-6 |
| Pubmed ID | |
| Authors |
Dan Zhou, Bonnie M. Alver, Shuang Li, Ryan A. Hlady, Joyce J. Thompson, Mark A. Schroeder, Jeong-Heon Lee, Jingxin Qiu, Philip H. Schwartz, Jann N. Sarkaria, Keith D. Robertson |
| Abstract |
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. 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 properly remodel their epigenome. Our integrative epigenomic and transcriptomic characterization reveals fundamentally distinct yet potentially targetable biologic features of GSCs that result from their distinct epigenomic landscapes. |
X Demographics
The data shown below were collected from the profiles of 16 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 31% |
| United Kingdom | 2 | 13% |
| Portugal | 1 | 6% |
| Canada | 1 | 6% |
| Germany | 1 | 6% |
| Unknown | 6 | 38% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 9 | 56% |
| Scientists | 5 | 31% |
| Science communicators (journalists, bloggers, editors) | 2 | 13% |
Mendeley readers
The data shown below were compiled from readership statistics for 106 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 106 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 27 | 25% |
| Researcher | 16 | 15% |
| Student > Bachelor | 10 | 9% |
| Student > Master | 10 | 9% |
| Student > Doctoral Student | 8 | 8% |
| Other | 10 | 9% |
| Unknown | 25 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 42 | 40% |
| Medicine and Dentistry | 11 | 10% |
| Agricultural and Biological Sciences | 7 | 7% |
| Neuroscience | 6 | 6% |
| Economics, Econometrics and Finance | 2 | 2% |
| Other | 8 | 8% |
| Unknown | 30 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 September 2018.
All research outputs
#4,661,764
of 25,382,440 outputs
Outputs from Genome Biology
#2,753
of 4,468 outputs
Outputs of similar age
#85,711
of 344,729 outputs
Outputs of similar age from Genome Biology
#29
of 38 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,468 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.6. This one is in the 38th percentile – i.e., 38% of its peers scored the same or lower than it.
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