Gene Set: MIKKELSEN_DEDIFFERENTIATED_STATE_UP

Standard name MIKKELSEN_DEDIFFERENTIATED_STATE_UP
Systematic name M1924
Brief description Genes up-regulated in partially reprogrammed and pluripotent cell populations (induced, iPS; and embryonic stem cells, ES) compared to parental lineage-commited cell lines.
Full description or abstract Somatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report an integrative genomic analysis of reprogramming of mouse fibroblasts and B lymphocytes. Lineage-committed cells show a complex response to the ectopic expression involving induction of genes downstream of individual reprogramming factors. Fully reprogrammed cells show gene expression and epigenetic states that are highly similar to embryonic stem cells. In contrast, stable partially reprogrammed cell lines show reactivation of a distinctive subset of stem-cell-related genes, incomplete repression of lineage-specifying transcription factors, and DNA hypermethylation at pluripotency-related loci. These observations suggest that some cells may become trapped in partially reprogrammed states owing to incomplete repression of transcription factors, and that DNA de-methylation is an inefficient step in the transition to pluripotency. We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18509334   Authors: Mikkelsen TS,Hanna J,Zhang X,Ku M,Wernig M,Schorderet P,Bernstein BE,Jaenisch R,Lander ES,Meissner A
Exact source Fig. 1: UP in partially reprogrammed iPS/ES
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform MOUSE_GENE_SYMBOL
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Version history 3.1: First introduced

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