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Status |
Public on Nov 01, 2023 |
Title |
Cell quiescence and reprogramming are distinctive features of pre-leukemic stem cells [H2Bgfp] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The leukemic stem cell concept is well established in B-acute lymphoblastic leukemia (B-ALL). However, the question of how a primary oncogene reprograms stem cell-like properties in committed B-cells and leads to a pre-neoplastic population remains unclear. Here, we used the PAX5-ELN oncogenic model to demonstrate a causal link between the differentiation blockade, the self-renewal and the emergence of pre-leukemic stem cells (pre-LSCs). Through multi-parametric immunophenotyping, we show that PAX5-ELN oncoprotein disrupts the differentiation of pre-leukemic cells by enforcing the IL7r/JAK-STAT signaling pathway. This disruption is associated with the induction of rare and quiescent pre-LSCs that sustain the leukemia-initiating activity, as assessed using the H2B-GFP model. Integration of transcriptomic and chromatin accessibility data reveals that those quiescent pre-LSCs lose B-cell identity and reactivate an immature molecular program, reminiscent of human B-ALL chemo-resistant cells. Collectively, our study sheds new lights on the biological mechanisms underlying the cell-of-origin of leukemia. We performed gene expression profiling analysis using data obtained from RNA-seq of quiescent or proliferative B-cells PEtg mice.
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Overall design |
Comparative gene expression profiling analysis of RNA-seq data for B-cell progenitors PEtg quiescent and proliferative H2B-GFP high = quiescent H2B-GFP low = proliferating
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Contributor(s) |
Gerby B, Fregona V |
Citation missing |
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Submission date |
Aug 10, 2022 |
Last update date |
Nov 01, 2023 |
Contact name |
Vincent Fregona |
Organization name |
INSERM
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Department |
31000
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Lab |
Centre de Recherche en Cancerologie de Toulouse
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Street address |
2 avenue hubert curien
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City |
TOULOUSE |
State/province |
Terres australes françaises |
ZIP/Postal code |
31100 |
Country |
France |
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Platforms (1) |
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Samples (10)
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This SubSeries is part of SuperSeries: |
GSE210926 |
Stem cell-like reprogramming is required for leukemia initiating activity in B-ALL |
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Relations |
BioProject |
PRJNA868329 |