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Selective eradication of leukemia cells with reprogramming factors (RNA-Seq)

ABSTRACT: We used RNA-seq to evaluate the global programme of gene expression after Dox inducible Yamanaka factors ectopic expression during this biological process.

ORGANISM(S): Mus musculus

PROVIDER: GSE121122 | GEO | 2019/09/23

REPOSITORIES: GEO

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Selective eradication of leukemia cells with reprogramming factors (ATAC-Seq)

Project description:We used ATAC-seq to evaluate the global programme of chromtain accessibility after Dox inducible Yamanaka factors ectopic expression during this biological process.

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Selective eradication of leukemia cells with reprogramming factors

Project description:Selective eradication of leukemia cells with reprogramming factors

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Targeting of apoptosis gene loci by reprogramming factors leads to selective eradication of leukemia cells.

Project description:Applying somatic cell reprogramming strategies in cancer cell biology is a powerful approach to analyze mechanisms of malignancy and develop new therapeutics. Here, we test whether leukemia cells can be reprogrammed in vivo using the canonical reprogramming transcription factors-Oct4, Sox2, Klf4, and c-Myc (termed as OSKM). Unexpectedly, we discover that OSKM can eradicate leukemia cells and dramatically improve survival of leukemia-bearing mice. By contrast, OSKM minimally impact normal hematopoietic cells. Using ATAC-seq, we find OSKM induce chromatin accessibility near genes encoding apoptotic regulators in leukemia cells. Moreover, this selective effect also involves downregulation of H3K9me3 as an early event. Dissection of the functional effects of OSKM shows that Klf4 and Sox2 play dominant roles compared to c-Myc and Oct4 in elimination of leukemia cells. These results reveal an intriguing paradigm by which OSKM-initiated reprogramming induction can be leveraged and diverged to develop novel anti-cancer strategies.

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Selective eradication of leukemia cells with reprogramming factors (RNA-Seq)

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Selective eradication of leukemia cells with reprogramming factors (ATAC-Seq)

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Aberrant DNA methylation reprogramming during iPS cell generation is dependent on the choice of reprogramming factors

Project description:we generate iPSCs from a common fibroblast cell source using either the Yamanaka factors (OCT4, SOX2, KLF4 and MYC) or the Thomson factors (OCT4, SOX2, NANOG and LIN28) and determined their genome-wide DNA methylation profiles. In addition to shared DNA methylation aberrations present in all our iPSCs, we identify Yamanaka-iPSC (Y-iPSCs)-specific and Thomson-iPSCs (T-iPSC)-specific recurrent aberrations. Bisulphite converted DNA from 9 iPS cells derived using Yamanaka factors (OSKM), 6 iPS cells derived using Thompson factors (OSLN), 2 parental fibroblasts and one embrionic ES cell were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

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