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STAMCELLER-Stamcelleforskning

Genome plasticity of somatic stem cells

Tildelt: kr 5,0 mill.

Chromatin organization in stem cells arises from distinct combinations of epigenetic marks resulting in genomic plasticity. Mesenchymal stem cells (MSCs) have received intense attention due to their perceived potential use in regenerative medicine. Nothin g is known, however, on epigenetic marks of MSCs, and on whether the epigenome reflects multipotent differentiation capacity. This proposal addresses this issue. We first hypothesize that MSCs of a given tissue are committed (pre-programmed) to a spec ific lineage by their epigenome. So if our hypothesis is correct, MSCs from of two distinct tissues (eg, adipose, muscle) should display a distinct epigenetic makeup at genes specifying adipogenesis and myogenesis, and exhibit different differentiation po tentials. To test this hypothesis, we will determine the extent of lineage commitment of adipose stem cells (ASCs) and muscle satellite cells (SatSCs) by DNA methylation and histone modification profiling. Epigenetic commitment of ASCs and SatSCs to adipo genic and myogenic lineages will be determined in in vitro differentiation studies. In vivo commitment will be assessed by in vivo imaging of transplanted Luc+GFP+ ASCs in mice and epigenetic analysis of retrieved cells. Our second hypothesis states that ASCs can be driven to a more pluripotent state by a reprogramming nuclear function, resulting in enhanced differentiation potential. We will determine whether ASCs can be epigenetically reprogrammed, then assess differentiation potential in vitro and in vivo. Epigenetic mapping of the cells before and after differentiation will validate of infer the hypothesis. Our expertise in ASC biology, epigenetic analyses (papers in press) and nuclear reprogramming will be supplemented by collaborations on embry onic stem cells, array technology, biocomputing and in vivo imaging to create a cross-disciplinary competence on stem cell epigenomics and differentiation within the Norwegian Stem Cell Network.

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STAMCELLER-Stamcelleforskning