A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets
University of California, San Francisco · Neurological Surgery
Abstract
Recent longitudinal studies of glioblastoma (GBM) have demonstrated a lack of apparent selection pressure for specific DNA mutations in recurrent disease. Single-cell lineage tracing has shown that GBM cells possess a high degree of plasticity. Together this suggests that phenotype switching, as opposed to genetic evolution, may be the escape mechanism that explains the failure of precision therapies to date. We profiled 86 primary-recurrent patient-matched paired GBM specimens with single-nucleus RNA, single-cell open-chromatin, DNA and spatial transcriptomic/proteomic assays. We found that recurrent GBMs are characterized by a shift to a mesenchymal phenotype. We show that the mesenchymal state is mediated…
Citation impact
- FWCI
- 27.03
- Percentile
- 100%
- References
- 62
Authors
13- LWLin WangCorresponding
University of California, San Francisco, Neurological Surgery
- JJJangham Jung
University of California, San Francisco, Neurological Surgery
- HBHusam Babikir
University of California, San Francisco, Neurological Surgery
- KSKarin Shamardani
University of California, San Francisco, Neurological Surgery
- SJSaket Jain
University of California, San Francisco, Neurological Surgery
Topics & keywords
- Biology
- Phenotype
- Cell
- Mesenchymal stem cell
- Paracrine signalling
- Cancer research
- Single-cell analysis
- Cell therapy
- Good health and well-being