Single-cell chromatin accessibility in glioblastoma delineates cancer stem cell heterogeneity predictive of survival
Guilhamon, P.; Kushida, M. M.; Nikolic, A.; Singhal, D.; MacLeod, G.; Tonekaboni, S. A. M.; Cavalli, F. M.; Arlidge, C.; Rajakulendran, N.; Rastegar, N.; Hao, X.; Hassam, R.; Smith, L. J.; Whetstone, H.; Coutinho, F. J.; Nadorp, B.; Ellestad, K. I.; Luchman, A. H.; Chan, J. A.; Shoichet, M. S.; Taylor, M. D.; Haibe-Kains, B.; Weiss, S.; Angers, S.; Gallo, M.; Dirks, P.; Lupien, M.
Show abstract
Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as Glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Distinct Tumor-TAM Interactions in IDH-Stratified Glioma Microenvironments unveiled by Single-Cell and Spatial Transcriptomics 98%
- Capture at the single cell level of metabolic modules distinguishing aggressive and indolent glioblastoma cells 96%
- Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population 94%
Similar papers in this journal
- Spatial transcriptomic analysis of Sonic Hedgehog Medulloblastoma identifies that the loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition 96%
- Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts 94%
- Retroelement co-option disrupts the cancer transcriptional programme 94%
Similar papers in this journal
Similar papers in this journal
- IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy 97%
- Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma 95%
- Single cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.