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- W3210702954 abstract "Cancers develop from the accumulation of somatic mutations, yet it remains unclear how oncogenic lesions cooperate to drive cancer progression. Using a mouse model harboring NRasG12D and EZH2 mutations that recapitulates leukemic progression, we employ single-cell transcriptomic profiling to map cellular composition and gene expression alterations in healthy or diseased bone marrows during leukemogenesis. At cellular level, NRasG12D induces myeloid lineage-biased differentiation and EZH2-deficiency impairs myeloid cell maturation, whereas they cooperate to promote myeloid neoplasms with dysregulated transcriptional programs. At gene level, NRasG12D and EZH2-deficiency independently and synergistically deregulate gene expression. We integrate results from histopathology, leukemia repopulation, and leukemia-initiating cell assays to validate transcriptome-based cellular profiles. We use this resource to relate developmental hierarchies to leukemia phenotypes, evaluate oncogenic cooperation at single-cell and single-gene levels, and identify GEM as a regulator of leukemia-initiating cells. Our studies establish an integrative approach to deconvolute cancer evolution at single-cell resolution in vivo." @default.
- W3210702954 created "2021-11-08" @default.
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- W3210702954 date "2021-11-03" @default.
- W3210702954 modified "2023-10-14" @default.
- W3210702954 title "Convergence of oncogenic cooperation at single-cell and single-gene levels drives leukemic transformation" @default.
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- W3210702954 doi "https://doi.org/10.1038/s41467-021-26582-4" @default.
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- W3210702954 hasPublicationYear "2021" @default.
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