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

TitleRapid induction of pluripotency genes after exposure of human somatic cells to mouse ES cell extracts.
Publication TypeJournal Article
Year of Publication2008
AuthorsBru T, Clarke C, McGrew MJ, Sang HM, Wilmut I, J Blow J
JournalExp Cell Res
Volume314
Issue14
Pagination2634-42
Date Published2008 Aug 15
ISSN1090-2422
KeywordsAnimals, Biological Markers, Cell Extracts, Cell Line, Cell Membrane Permeability, Embryonic Stem Cells, Gene Expression Regulation, Histones, Homeodomain Proteins, Humans, Lamin Type A, Mice, Octamer Transcription Factor-3, Pluripotent Stem Cells, Promoter Regions, Genetic, Protein Binding, Protein Biosynthesis, RNA Polymerase II, Transcription, Genetic, Xenopus
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 II 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 reprogramming somatic cells to a pluripotent state without genetically altering them.

DOI10.1016/j.yexcr.2008.05.009
Alternate JournalExp. Cell Res.
PubMed ID18571647
PubMed Central IDPMC2577761
Grant ListA3135 / / Cancer Research UK / United Kingdom
A7399 / / Cancer Research UK / United Kingdom
C303/A3135 / / Cancer Research UK / United Kingdom
C303/A7399 / / Cancer Research UK / United Kingdom
G20421 / / Biotechnology and Biological Sciences Research Council / United Kingdom
G20421 / / Biotechnology and Biological Sciences Research Council / United Kingdom