Title: Intrinsic cell memory reinforces myogenic commitment of pericyte-derived iPSCs
Authors: Quattrocelli, Mattia ×
Palazzolo, Giacomo
Floris, Guiseppe
Schöffski, Patrick
Anastasia, Luigi
Orlacchio, Aldo
Vandendriessche, Thierry
Chuah, Marinee
Cossu, Giulio
Verfaillie, Catherine
Sampaolesi, Maurilio #
Issue Date: Apr-2011
Publisher: Longman
Series Title: Journal of Pathology vol:223 issue:5 pages:593-603
Article number: 10.1002/path.2845
Abstract: 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 αsg-KO mice, can efficiently participate to skeletal muscle regeneration and restore αsg 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.
ISSN: 0022-3417
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
Hematology Section (-)
Molecular and Vascular Biology
Interdepartemental Stem Cell Institute (-)
× corresponding author
# (joint) last author

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