Glioblastoma vessel co-option occurs as a resistance mechanism to chemoradiation via induction of a persister cell state
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA906031 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22427413_1.fastq.gz | Fastqsanger.gz | |||
| SRR22427413_2.fastq.gz | Fastqsanger.gz | |||
| SRR22427414_1.fastq.gz | Fastqsanger.gz | |||
| SRR22427414_2.fastq.gz | Fastqsanger.gz | |||
| SRR22427415_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 76 |
Similar Datasets
Project description:Glioblastoma (GB) is one of the deadliest types of human cancer. Recurrence after chemoradiation is mostly caused by regrowth of highly invasive and resistant cells. There is an urgent need to better understand the underlying GB mechanisms of chemoradiation resistance and tumor spreading. Using a combination of transcriptomic analysis, longitudinal imaging, organotypic cultures, functional assays, animal studies and clinical data analyses, we demonstrated that chemoradiation and brain vasculature induce a transition to an invasive functional cell state that we named VC-Resist. Better cell survival, G2M-arrest, senescence/stemness pathways’ induction and YAP activation make this GB cell state more resistant to therapy. Notably, these persister GB cells are highly vessel co-opting, allowing homing to the perivascular niche, which in turn increases their transition to this cell state. These findings demonstrate how vessel co-option, the perivascular niche, and GB cell plasticity jointly drive resistance during GB recurrence.
2024-01-01 | GSE218860 | GEO
Project description:Vessel co-option is an alternative mode of tumor vascularization, which contributes to resistance to anti-angiogenic therapy (AAT). In contrast to vessel sprouting (angiogenesis), knowledge about the mechanisms underlying vessel co-option is minimal, precluding therapeutic strategies. We therefore single-cell RNA-sequenced 31,964 cells from a murine lung metastasis model with vessel co-option, characterized by resistance to AAT. Unexpectedly, co-opted endothelial cells (ECs) were transcriptomically indistinguishable from healthy ECs and lacked an activation signature, while co-opted pericytes expressed a quiescence signature, in contrast to activated pericytes during angiogenesis. Compared with cancer cells during angiogenesis, co-opting cancer cells were phenotypically more diverse and enriched in invasive subpopulations. Together, these data reveal new insight into vessel co-option, with possible implications for the development of therapeutic targets.
2021-06-15 | E-MTAB-9227 | biostudies-arrayexpress
Project description:Single cell transcriptomics profiling of vessel co-option
| PRJEB39195 | ENA
Project description:The LncRNA promotes vessel co-option mediated antiagiogenic therapies (AATs) resistance
| PRJNA914872 | ENA
Project description:Bacterial persister cells are phenotypic variants of regular cells that are tolerant to antibiotics. High-persister (hip) mutants of Mycobacterium tuberculosis produce 10- to 1,000-fold more persister cells than the wild type strain when challenged with various antibiotics. Comparison of gene expression pattern of the hip mutants may provide clues as to the genetic mechanisms underlying persister formation. Transcriptome analysis will provide information on what differentiates M. tuberculosis hip strains from regular strains, which will be useful in the development of anti-persister therapy for persister cell eradication. Twelve independent M. tuberculosis hip mutants and the wild type strain were grown to stationary phase in duplicate. To avoid analyzing the drug effect, total RNA was extracted from the cultures prior to the addition of antibiotic for hybridization to Affymetrix microarrays. Data analysis was performed by comparing the hip mutants to the wild type control.
2014-04-07 | E-GEOD-55647 | biostudies-arrayexpress
Project description:Gene expression profiling to predict outcome after chemoradiation in head and neck cancer Purpose. The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis. Materials and Methods. We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict local control, locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested. Results. Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end-points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Also previously published signatures with prognostic value have been tested. Conclusion. Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.
2008-02-19 | E-NCMF-8 | biostudies-arrayexpress
Project description:Analysis of peripheral circulating mRNA expression levels in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma. The hypothesis test was that chemoradiation alters the circulating mRNA expression profiles and the profiling is predictive of pathological response. Results provide information on the response of circulating mRNAs to chemoradiation and identify novel biomarkers or targets in esophageal squamous cell carcinoma. Total RNA obtained from peripheral whole blood before and after neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. 21 patients with 42 samples were analyzed. The expression profiles from pathological complete responders were compared to non-complete responders.
2014-01-01 | E-GEOD-43519 | biostudies-arrayexpress
Project description:Analysis of peripheral circulating mRNA expression levels in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma. The hypothesis test was that chemoradiation alters the circulating mRNA expression profiles and the profiling is predictive of pathological response. Results provide information on the response of circulating mRNAs to chemoradiation and identify novel biomarkers or targets in esophageal squamous cell carcinoma.
2014-01-01 | GSE43519 | GEO
Project description:Acquired drug resistance prevents targeted cancer therapy from achieving stable and complete responses. Emerging evidence implicates a key role for nonmutational mechanisms including changes in cell state during early stages of acquired drug resistance. Targeting nonmutational resistance may therefore present a therapeutic opportunity to eliminate residual surviving tumor cells and impede relapse. A variety of cancer cell lines harbor quiescent, reversibly drug-tolerant âpersisterâ cells which survive cytotoxic drugs including targeted therapies and chemotherapies. These persister cells survive drug through nonmutational mechanisms which are poorly understood. Specifically targeting persister cells is a promising strategy to prevent tumor relapse. We sought to identify therapeutically exploitable vulnerabilities in persister cells using the HER2-amplified breast cancer line BT474 as an experimental model. Similar to other persister cell models, upon treatment with the HER2 inhibitor lapatinib (2uM concentration) for nine or more days, the majority of BT474 cells die, revealing a small population of quiescent surviving persister cells. Removal of lapatinib allows the persister cells to regrow and to re-acquire sensitivity to lapatinib. Subsequent lapatinib treatment re-derives persister cells. The reversibility of persister cell drug resistance indicates a nonmutational resistance mechanism. Here we provide RNAseq gene expression profiling data generated from parental BT474 cells compared to BT474 persister cells generated from nine days of treatment with 2 uM lapatinib. These data can be used to identify genes and pathways which are upregulated in persister cells, revealing potential therapeutic targets. 3 biological replicates of BT474 persister cells, two biological replicates of BT474 parental cells
2016-07-28 | E-GEOD-84896 | biostudies-arrayexpress
Project description:Persisters are cells which evade stresses like antibiotics and which are characterized by reduced metabolism and a lack of genetic alterations required to achieve this state. We showed previously that MqsR and MqsA of Escherichia coli are a toxin-antitoxin pair that influence cell physiology (e.g., biofilm formation and motility) via RNase activity as well as through regulation of toxin CspD. Here, we show that deletion of the mqsRA locus decreases persister cell formation and, consistent with this result, overexpression of MqsR increases persister cell formation. Furthermore, toxins Hha, CspD, and HokA increase persister cell formation. In addition, by overproducing MqsR in a series of isogenic mutants, we show that Hha and CspD are necessary for persister cell formation via MqsR overexpression. Surprisingly, Hfq, a small RNA chaperone, decreases persistence. A whole-transcriptome study shows that Hfq induces transport-related genes (oppA, oppB, oppC, oppD, oppF, and dppA), outer membrane protein-related genes (ybfM and ybfN), toxins (hha), and proteases (clpX, clpP, and lon). Taken together, these results indicate that toxins CspD and Hha influence persister cell formation via MqsR and that Hfq plays an important role in the regulation of persister cell formation via regulation of transport or outer membrane proteins. Strains: E. coli BW25113 K-12 hfq deleted mutant vs. wild-type Medium: LB Culture: Planktonic cell grown OD=0.5, adjusted OD=1.0, and then exposed to 100 ug/mL ampicillin for 2 h.
2009-11-07 | E-GEOD-18852 | biostudies-arrayexpress