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Reprogramming efficiency and quality of induced Pluripotent Stem Cells (iPSCs) generated from muscle-derived fibroblasts of mdx mice at different ages
Author(s) -
Bo Wang,
Yuko MiyagoeSuzuki,
Erica Yada,
Naoki Ito,
Takashi Nishiyama,
Miho Nakamura,
Yusuke Ono,
Norio Motohashi,
Makoto Segawa,
S. Masuda,
Shin’ichi Takeda
Publication year - 2011
Publication title -
plos currents
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.282
H-Index - 49
ISSN - 2157-3999
DOI - 10.1371/currents.rrn1274
Subject(s) - induced pluripotent stem cell , reprogramming , homeobox protein nanog , duchenne muscular dystrophy , microbiology and biotechnology , mdx mouse , muscular dystrophy , stem cell , biology , embryonic stem cell , medicine , cell , dystrophin , genetics , gene
Induced pluripotent stem cells (iPSCs) hold promise as a potential treatment for Duchenne muscular dystrophy (DMD). To determine the impact of the donor’s age on reprogramming, we generated iPSCs from muscle-derived fibroblasts (MuFs) of mdx mice aged 6 weeks, 6 months, and 14 months. MuFs from 14-month-old mdx mice showed lower proliferative activity and lower reprogramming efficiency, compared with those from younger mdx mice. Furthermore, iPSCs derived from 14-month-old mdx mice (14m-MuF-iPSCs) gradually lost Nanog expression, and regressed in conventional ES medium during passages. Interestingly, inhibition of TGF-β signaling and BMP signaling stabilized Nanog expression and promoted self-renewal of 14m-MuF-iPSCs. Finally, rescued mdx-derived iPSCs efficiently differentiated into the skeletal muscle lineage.

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