The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
The Phenotypes of Proliferating Glioblastoma Cells Reside on a Single Axis of Variation
Open accessAbstract
Although tumor-propagating cells can be derived from glioblastomas (GBM) of the proneural and mesenchymal subtypes, a glioma stem-like cell (GSC) of the classic subtype has not been identified. It is unclear whether mesenchymal GSCs (mGSC) and/or proneural GSCs (pGSC) alone are sufficient to generate the heterogeneity observed in GBM. We performed single-cell/single-nucleus RNA sequencing of 28 gliomas, and single-cell ATAC sequencing for 8 cases. We found that GBM GSCs reside on a single axis of variation, ranging from proneural to mesenchymal. In silico lineage tracing using both transcriptomics and genetics supports mGSCs as the progenitors of pGSCs. Dual inhibition of pGSC-enriched and mGSC-enriched growth and survival pathways provides a more complete treatment than combinations targeting one GSC phenotype alone. This study sheds light on a long-standing debate regarding lineage relationships among GSCs and presents a paradigm by which personalized combination therapies can be derived from single-cell RNA signatures, to overcome intratumor heterogeneity. Significance: Tumor-propagating cells can be derived from mesenchymal and proneural glioblastomas. However, a stem cell of the classic subtype has yet to be demonstrated. We show that classic-subtype gliomas are comprised of proneural and mesenchymal cells. This study sheds light on a long-standing debate regarding lineage relationships between glioma cell types. See related commentary by Fine, p. 1650. This article is highlighted in the In This Issue feature, p. 1631
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Metadata
- Authors
- Wang, L., Babikir, H., Müller, S., Yagnik, G., Shamardani, K., Catalan, F., Kohanbash, G., Alvarado, B., Di Lullo, E., Kriegstein, A., Shah, S., Wadhwa, H., Chang, S. M., Phillips, J. J., Aghi, M. K., & Diaz, A. A.
- Venue
- Cancer Discovery
- Published
- 2019-12-01
- Volume
- 9
- Issue
- 12
- Pages
- 1708-1719
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2975379509
- Cited by
- 363
- References
- 31
- FWCI
- 19.68
- Type
- journal article
- Language
- en
- Open access
- green
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- Wang, L., Babikir, H., Müller, S., Yagnik, G., Shamardani, K., Catalan, F., Kohanbash, G., Alvarado, B., Di Lullo, E., Kriegstein, A., Shah, S., Wadhwa, H., Chang, S. M., Phillips, J. J., Aghi, M. K., & Diaz, A. A. (2019). The Phenotypes of Proliferating Glioblastoma Cells Reside on a Single Axis of Variation. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-19-0329
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