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In Vivo Profiling of Leukemic Stem Cell Fitness

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE121354 | GEO | 2019/10/16

REPOSITORIES: GEO

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Project description:winner&loser

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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

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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.

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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.

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Single cell RNAseq of murine gliomas induced by PDGFB overexpression

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