Rapid induction of pluripotency genes after exposure of human somatic cells to mouse ES cell extracts

Thierry Bru, Catriona Clarke, Michael J. McGrew, Helen M. Sang, Ian Wilmut, J. Julian Blow

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    Abstract

    The expression of 4 pluripotency genes (Oct4, Sox2, c-Myc and Klf4) in mouse embryonic fibroblasts can reprogramme them to a pluripotent state. We have investigated the expression of these pluripotency genes when human somatic 293T cells are permeabilized and incubated in extracts of mouse embryonic stem (ES) cells. Expression of all 4 genes was induced over 1-8 h. Gene expression was associated with loss of repressive histone H3 modifications and increased recruitment of RNA polymerase 11 at the promoters. Lamin A/C, which is typically found only in differentiated cells, was also removed from the nuclei. When 293T cells were returned to culture after exposure to ES cell extract, the expression of the pluripotency genes continued to rise over the following 48 h of culture, suggesting that long-term reprogramming of gene expression had been induced. This provides a methodology for studying the de-differentiation of somatic cells that can potentially lead to an efficient way of reprograrnming somatic cells to a pluripotent state without genetically altering them. (C) 2008 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)2634-2642
    Number of pages9
    JournalExperimental Cell Research
    Volume314
    Issue number14
    DOIs
    Publication statusPublished - 15 Aug 2008

    Keywords

    • reprogramming
    • pluripotent
    • embryonic stem cells
    • gene expression
    • oct-4 expression levels
    • EMBRYONIC STEM-CELLS
    • IN-VITRO
    • DEFINED FACTORS
    • NUCLEI
    • FIBROBLASTS
    • EXPRESSION
    • CARCINOMA
    • NANOG
    • OCT4
    • DIFFERENTIATION

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