These authors contributed equally to this work.
Intrinsic cell memory reinforces myogenic commitment of pericyte-derived iPSCs†
Article first published online: 21 FEB 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 223, Issue 5, pages 593–603, April 2011
How to Cite
Quattrocelli, M., Palazzolo, G., Floris, G., Schöffski, P., Anastasia, L., Orlacchio, A., Vandendriessche, T., Chuah, M. K., Cossu, G., Verfaillie, C. and Sampaolesi, M. (2011), Intrinsic cell memory reinforces myogenic commitment of pericyte-derived iPSCs. J. Pathol., 223: 593–603. doi: 10.1002/path.2845
No conflicts of interest were declared.
- Issue published online: 10 MAR 2011
- Article first published online: 21 FEB 2011
- Accepted manuscript online: 20 DEC 2010 04:04AM EST
- Manuscript Accepted: 14 DEC 2010
- Manuscript Revised: 13 DEC 2010
- Manuscript Received: 2 SEP 2010
- FWO-Odysseus Programme. Grant Number: G.0907.08
- Research Council of the University of Leuven. Grant Number: OT/09/053
- Wicka Funds. Grant Number: zkb8720
- Italian Ministry of University and Scientific Research. Grant Numbers: PRIN 2005067555_003, PRIN 2008RENT8T_003, CARIPLO Nos 2007.5639, 2008.2005
- EC. Grant Number: CARE-MI
- muscular dystrophy;
- epigenetic memory
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.