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Intrinsic cell memory reinforces myogenic commitment of pericyte‐derived iPSCs
Author(s) -
Quattrocelli Mattia,
Palazzolo Giacomo,
Floris Giuseppe,
Schöffski Patrick,
Anastasia Luigi,
Orlacchio Aldo,
Vandendriessche Thierry,
Chuah Marinee KL,
Cossu Giulio,
Verfaillie Catherine,
Sampaolesi Maurilio
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2845
Subject(s) - induced pluripotent stem cell , biology , microbiology and biotechnology , population , reprogramming , progenitor cell , skeletal muscle , stem cell , embryonic stem cell , cell , genetics , anatomy , medicine , gene , environmental health
Mesoangioblasts (MABs) are a subset of muscle‐derived pericytes able to restore dystrophic phenotype in mice and dogs. However, their lifespan is limited and they undergo senescence after 25–30 population doublings. Recently, induced pluripotent stem cells (iPSCs) generated from reprogrammed fibroblasts have been demonstrated to have in vitro and in vivo myogenic potential when sorted for the SM/C‐2.6 antigen. Furthermore, chimeric mice from mdx‐iPSCs (DYS‐HAC) cells showed tissue‐specific expression of dystrophin. Nevertheless, myogenic differentiation protocols and the potential of iPSCs generated from different cell sources still present unanswered questions. Here we show that iPSCs generated from prospectively sorted MABs (MAB‐iPSCs) are pluripotent as fibroblast‐derived iPSCs (f‐iPSCs). However, both teratoma formation and genetic cell manipulation assays identify a durable epigenetic memory in MAB‐iPSCs, resulting in stronger myogenic commitment. Striated muscle tissue accounts for up to 70% of MAB‐iPSC teratomas. Moreover, transfection with Pax3 and Pax7 induces a more robust myogenic differentiation in MAB‐iPSCs than in f‐iPSCs. A larger amount of CD56 + progenitors can be sorted from the MAB‐iPSCs differentiating pool and, after transplantation into α sg‐KO mice, can efficiently participate to skeletal muscle regeneration and restore α sg expression. Our data strongly suggest that iPSCs are a heterogeneous population and, when generated from myogenic adult stem cells, they exhibit a stronger commitment, paving the way for creating custom‐made cell protocols for muscular dystrophies. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.