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Accueil du site > Animations Scientifiques > Séminaires 2008 > Epigenetic programming of mesenchymal stem cells from adipose tissue

Epigenetic programming of mesenchymal stem cells from adipose tissue

Orateur :

Philippe Collas, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

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Mesenchymal stem cells, including adipose tissue stem cells (ASCs) can differentiate into various cell types, primarily of the mesodermal lineage. Multi-lineage differentiation capacity is enabled by epigenetic marks which create a chromatin configuration compatible with potential for gene activation. We have examined the DNA methylation pattern of ASCs and other MSC types and showed adipogenic promoters are CpG hypomethylated, in contrast to, non-adipogenic, lineage-specific promoters which are more methylated. Current genome-wide DNA methylation studies aim at providing a more global picture of a link between promoter DNA methylation and lineage commitment. Chromatin immunoprecipitation analysis of ASCs reveals that adipogenic promoters are primed for activation by trimethylation of H3K4 but held in check by trimethylation of H3K27, a target for polycomb group proteins. Differentiation triggers demethylation H3K27 and acetylation of H3K9 on adipogenic promoters. Upon senescence however, inhibition of differentiation correlates with promoter targeting of polycomb proteins, conceivably as a means of (globally ?) shutting down transcription. We propose that DNA hypomethylation together with H3K4 and K27 trimethylation on adipogenic promoters constitutes a molecular signature of ASCs that programs ASCs for adipogenesis preferentially over other pathways. This configuration may poise genes for transcriptional activation upon differentiation.

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