Efficient generation of iPS cells from skeletal muscle stem cells.
Reprogramming of somatic cells into inducible pluripotent stem cells generally occurs at low efficiency, although what limits reprogramming of particular cell types is poorly understood. Recent data suggest that the differentiation status of the cell targeted for reprogramming may influence its susceptibility to reprogramming as well as the differentiation potential of the induced pluripotent stem (iPS) cells that are derived from it. To assess directly the influence of lineage commitment on iPS cell derivation and differentiation, we evaluated reprogramming in adult stem cell and mature cell populations residing in skeletal muscle. Our data using clonal assays and a second-generation inducible reprogramming system indicate that stem cells found in mouse muscle, including resident satellite cells and mesenchymal progenitors, reprogram with significantly greater efficiency than their more differentiated daughters (myoblasts and fibroblasts). However, in contrast to previous reports, we find no evidence of biased differentiation potential among iPS cells derived from myogenically committed cells. These data support the notion that adult stem cells reprogram more efficiently than terminally differentiated cells, and argue against the suggestion that "epigenetic memory" significantly influences the differentiation potential of iPS cells derived from distinct somatic cell lineages in skeletal muscle.
Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, Massachusetts, United Stated of America.
Kah Yong
KY
Tan
Sarah
S
Eminli
Simone
S
Hettmer
Konrad
K
Hochedlinger
Amy J
AJ
Wagers
D050156:Adipogenesis; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins