Dissecting direct reprogramming through integrative genomic analysis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-07-03

AUTHORS

Tarjei S. Mikkelsen, Jacob Hanna, Xiaolan Zhang, Manching Ku, Marius Wernig, Patrick Schorderet, Bradley E. Bernstein, Rudolf Jaenisch, Eric S. Lander, Alexander Meissner

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. More... »

PAGES

49

References to SciGraph publications

Journal

TITLE

Nature

ISSUE

7200

VOLUME

454

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature07056

    DOI

    http://dx.doi.org/10.1038/nature07056

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1037743725

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18509334


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