Characterization of quiescent subpopulations and proliferative compartments in glioblastoma
Mihalas, A.; Mitchell, K.; Arora, S.; O'Connor, S.; Patel, A.; Plaisier, C. L.; PADDISON, P.
Show abstract
Glioblastoma (GBM) quiescent (Q) cell populations are hypothesized to contain cancer stem-like cells (CSC) that drive tumor growth, cellular heterogeneity, and recurrence. However, GBM tumors do not neatly resolve into developmental hierarchies and Q stem-like activities are difficult to assess. Here, we evaluated tumor Q subpopulations in patient-derived GBM xenograft tumors using live cell reporters, DNA label retention assays, and single cell genomics. Compared to adult neural stems cells (NSCs), GBM Q populations contain hybrid transcriptional states composed of networks found in both dormant and activated adult NSCs, resulting in constitutive expression of key Q egress transcription factors and their targets (e.g., AP-1 and CCND1/2). As a result, even the longest Q-residing cells ([~]12 days) in xenograft tumors continuously cycle and fail to enter dormant Q states. We provide evidence and hypothesize that transient Q states in primary tumors arise as part of distinct proliferative compartments rather than deterministic developmental hierarchies driven by CSC activity. We further speculate that increases in basal translation rates drive Q instability in GBM tumors.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity 96%
- The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells 94%
- Comparative molecular life history of spontaneous canine and human gliomas 94%
Similar papers in this journal
- Co-regulation and functional cooperativity of FOXM1 and RHNO1 bidirectional genes in ovarian cancer 94%
- An NKX2-1/ERK/WNT feedback loop modulates gastric identity and response to targeted therapy in lung adenocarcinoma 94%
- Transient regulation of focal adhesion via Tensin3 is required for nascent oligodendrocyte differentiation 94%
Similar papers in this journal
- Medulloblastoma Group 3 and 4 Tumors Comprise a Clinically and Biologically Significant Expression Continuum Reflecting Human Cerebellar Development 95%
- Cilium induction triggers differentiation of glioma stem cells 94%
- Excessive E2F transcription in single cancer cells precludes transient cell cycle exit after DNA damage. 94%
Similar papers in this journal
- WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma 96%
- The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma 93%
- Mouse Cortical Cellular Diversification Through Lineage Progression of Radial Glia 93%
Similar papers in this journal
- The epigenetic evolution of gliomas is determined by their IDH1 mutation status and treatment regimen 94%
- Distinct cell adhesion signature defines glioblastoma myeloid-derived suppressor cell subsets 94%
- Leveraging Allele-Specific Expression for Therapeutic Response Gene Discovery in Glioblastoma. 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.