| Title |
Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2
|
|---|---|
| Published in |
Cell Reports, October 2017
|
| DOI | 10.1016/j.celrep.2017.10.009 |
| Pubmed ID | |
| Authors |
Aram S. Modrek, Danielle Golub, Themasap Khan, Devin Bready, Jod Prado, Christopher Bowman, Jingjing Deng, Guoan Zhang, Pedro P. Rocha, Ramya Raviram, Charalampos Lazaris, James M. Stafford, Gary LeRoy, Michael Kader, Joravar Dhaliwal, N. Sumru Bayin, Joshua D. Frenster, Jonathan Serrano, Luis Chiriboga, Rabaa Baitalmal, Gouri Nanjangud, Andrew S. Chi, John G. Golfinos, Jing Wang, Matthias A. Karajannis, Richard A. Bonneau, Danny Reinberg, Aristotelis Tsirigos, David Zagzag, Matija Snuderl, Jane A. Skok, Thomas A. Neubert, Dimitris G. Placantonakis |
| Abstract |
Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis. |
X Demographics
The data shown below were collected from the profiles of 13 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 | 38% |
| France | 1 | 8% |
| Portugal | 1 | 8% |
| Unknown | 6 | 46% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 11 | 85% |
| Scientists | 1 | 8% |
| Science communicators (journalists, bloggers, editors) | 1 | 8% |
Mendeley readers
The data shown below were compiled from readership statistics for 121 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 121 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 24 | 20% |
| Student > Master | 16 | 13% |
| Researcher | 15 | 12% |
| Student > Bachelor | 10 | 8% |
| Student > Doctoral Student | 7 | 6% |
| Other | 13 | 11% |
| Unknown | 36 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 39 | 32% |
| Agricultural and Biological Sciences | 14 | 12% |
| Medicine and Dentistry | 10 | 8% |
| Neuroscience | 5 | 4% |
| Immunology and Microbiology | 3 | 2% |
| Other | 10 | 8% |
| Unknown | 40 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. 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 13 July 2018.
All research outputs
#5,341,501
of 25,382,440 outputs
Outputs from Cell Reports
#8,350
of 12,965 outputs
Outputs of similar age
#86,398
of 331,218 outputs
Outputs of similar age from Cell Reports
#195
of 297 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 78th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
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We're also able to compare this research output to 297 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.