Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bulk RNAseq of murine gliomas driven by overexpression of PDGFB

ABSTRACT: Glioblastoma progression remains elusive, especially in its first stages. Here, by simultaneous transfer of PDGFB and genetic barcode in mouse brain, we triggered gliomagenesis in univocally labelled cells in vivo, hence enabling direct tracing of glioblastoma evolution from the earliest possible stage. We observed an unexpectedly high incidence of clonal extinction events and progressive clonal size divergence, even after the acquisition of a malignant phenotype. Computational modelling suggests these dynamics as the consequence of a clonal-based cell-cell competition. Bulk and single-cell transcriptome analyses, coupled to lineage tracing, revealed that the strongest correlation with clonal size unbalancing is shown by Myc transcriptional targets. Additionally, higher levels of Myc signalling discriminate "winner" from "loser" clones in early gliomagenesis. These results agree with recent understanding of the Myc-mediated induction of supercompetitive phenotype in mammalian embryo. Our findings shed light on aspects of glioblastoma evolution inaccessible by conventional retrospective approaches and highlight the potential of the combined use of clonal tracing and transcriptomic analyses in this field.

ORGANISM(S): Mus musculus

PROVIDER: GSE189517 | GEO | 2023/07/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Single cell RNAseq of murine gliomas induced by PDGFB overexpression

Project description:Glioblastoma progression remains elusive, especially in its first stages. Here, by simultaneous transfer of PDGFB and genetic barcode in mouse brain, we triggered gliomagenesis in univocally labelled cells in vivo, hence enabling direct tracing of glioblastoma evolution from the earliest possible stage. We observed an unexpectedly high incidence of clonal extinction events and progressive clonal size divergence, even after the acquisition of a malignant phenotype. Computational modelling suggests these dynamics as the consequence of a clonal-based cell-cell competition. Bulk and single-cell transcriptome analyses, coupled to lineage tracing, revealed that the strongest correlation with clonal size unbalancing is shown by Myc transcriptional targets. Additionally, higher levels of Myc signalling discriminate "winner" from "loser" clones in early gliomagenesis. These results agree with recent understanding of the Myc-mediated induction of supercompetitive phenotype in mammalian embryo. Our findings shed light on aspects of glioblastoma evolution inaccessible by conventional retrospective approaches and highlight the potential of the combined use of clonal tracing and transcriptomic analyses in this field.

2023-07-18 | GSE189577 | GEO

Genomics of colony founding in fire ants - pleo2

Project description:This experiment was performed to investigate the effect of the manipulation of social rank on gene expression. Fire ants newly mated queens were paired and placed in nesting chambers. After emergence of workers, queensM-^R behavior was monitored. Once the behavioral observation revealed the social rank of the two cofoundresses (winners and losers), queens were weighed again and re-paired with a different partner. We created the following three groups of queens: a) winner + winner (similar weight), b) loser + loser (similar weight), and c) winner + loser (different weights). Again, we monitored the behavior until the social rank of the newly coupled specimens was evident and we collected 4 new behavioral phenotypes in the same way as above: a) winners switched into losers (win/los), b) losers switched into winners (los/win), c) continuing winners (win/win) and d) continuing losers (los/los).

2013-08-21 | E-MEXP-3898 | biostudies-arrayexpress

In Vivo Profiling of Leukemic Stem Cell Fitness

Project description:By transplanting in competition multiple pre-leukemic clones in a cohort of primary recipients, we observed emergence of dominant clones during the development of AML. By sampling “winner” clones at different time points, we could observe the gradual acquisition a of cell-intrinsic growth advantage that was preserved in secondary transplantation, whereas control “loser” clones grew at a significantly lower rate. Functional characterization of the winner clones demonstrated a higher engraftment rate in vivo, whereas the self-renewal potential and growth rate in vitro was similar among winner and loser clones. By comparing the gene expression profile of leukemic stem cells isolated from various clones, we observed that the most aggressive clones share a common signature characterized by activation of multiple metabolic pathways, such as steroid biosynthesis and response to oxidative stress.

2019-10-16 | GSE121354 | GEO

RNA sequencing of winner and loser hPSCs grown in either separate culture or upon co-culture.

Project description:The observation that human Pluripotent Stem Cells (hPSCs) may acquire non-random genetic changes during prolonged culture is a major concern for their use in regenerative medicine and disease modelling. The mechanisms through which genetically variant cells are selected for in culture remain poorly characterized. We have shown that the dominance of variant hPSCs with enhanced growth rates is enhanced through competitive interactions resulting in the elimination of the slower growing loser population. This experiment compares the gene expression of winner (H7v1,12,17q,20q-GFP) and loser (H7v1q) grown either in separate culture or competitively in co-culture together.

2021-03-18 | E-MTAB-10193 | biostudies-arrayexpress

Distinct modes of cell competition shape mammalian tissue morphogenesis

Project description:Cell competition (CC)—the sensing and elimination of less fit “loser” cells by neighbouring “winner” cells—was first described in Drosophila. Although proposed as a selection mechanism to optimize tissue and organ development, its evolutionary generality remains unclear. Here, by employing live-imaging, lineage-tracing, single cell transcriptomics and genetics, we unearth two intriguing CC mechanisms that sequentially shape and maintain stratified tissue architecture during mouse skin development. Early in embryonic epidermis, winner progenitors within the single-layered epithelium kill and clear neighbouring losers by engulfment. Upon stratification and skin barrier formation, the basal layer instead expels losers through a homeostatic upward flux of differentiating progeny. This CC switch is physiologically relevant, as when it is perturbed, so too is barrier formation. Our findings establish CC as a selective force to optimize function of a vertebrate tissue, but also illuminate how a tissue dynamically adjusts its CC strategies to preserve fitness as it encounters increased architectural complexity during morphogenesis.

2019-05-31 | GSE128241 | GEO

RNA-seq analysis of mutations inducing the loser status in Drosophila wing discs

Project description:In order to investigate the mechanisms of cell competition, we analyzed the molecular differences between the prospective winner and loser cells in Drosophila wing discs. For this purpose we analyzed RNA-seq profiles generated for wild-type cells (prospective winners) and cells mutant for RpS3 and mahj, genes seemingly functionally unrelated, yet both causing the loser phenotype. As an interesting reference, we also generated data from cells with mutations in RpS15, which, like RpS3, is a ribosomal gene but itself does not trigger cell competition. Through in depth analysis we homed in on the subset of genes misregulated in both prospective loser cells mutants, which defines "the molecular signature of prospective loser cells". Additionally, we provide RNA-seq data for RpS3 mutant discs upon inhibition of the JNK signalling pathway (by overexpression of the pathway inhibitor puckered) and compare this to reference RpS3 mutant cells, hence identifying those genes in RpS3 mutants that are differentially expressed in a JNK-dependent manner.

2017-03-16 | GSE92431 | GEO

Homo sapiens

Project description:Clonal Evolution of Glioblastoma under Therapy

| PRJNA320312 | ENA

RNA-seq analysis of CncC (Nrf2) over-expression to induce the loser status in Drosophila wing discs

Project description:To investigate the mechanisms of cell competition, we analysed the molecular differences between wild type and mild CncC (Nrf2) over-expressing causing the loser phenotype in Drosophila wing discs. We then compared the genes differentially expressed in these conditions to our previously identified ‘loser signature’ which reveal a significant overlap. From this later comparison, we raised a list of 121 up-regulated genes to conduct a cell competition screen using PECAn (Pipeline for Enhanced Clonal Analysis) for automating analysis of mosaic experiment.

2023-04-06 | GSE181165 | GEO

RNA sequencing of winner and loser hPSCs grown in either separate culture or upon co-culture.

Project description:RNA sequencing of winner and loser hPSCs grown in either separate culture or upon co-culture.

| PRJEB43508 | ENA

Single RNA-Seq on GBM cells from NPCTKO mouse models

Project description:Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells, to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Single-cell RNA sequencing showed that patterns of copy-number variations (CNVs) of mural cells and endothelial cells were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Furthermore, lineage tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, GBM cells did not give rise to non-neural cell types in the brain. Intriguingly, GBM cells could randomly express mesenchymal markers, including those for mural cells, during gliomagenesis. Most importantly, single-cell CNV analysis of human GBM specimens also strongly suggested that GBM cells and vascular cells are separate lineages. Instead, non-neural cell types expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.

2022-07-07 | GSE190154 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data