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Physiol. Genomics 37: 35-42, 2009. First published December 30, 2008; doi:10.1152/physiolgenomics.00051.2008
1094-8341/09 $8.00
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Received 11 March 2008; accepted in final form 23 December 2008.
Physiological Genomics 37:35-42 (2009)
1094-8341/09 $8.00 © 2009 American Physiological Society

Transcriptional and functional differences in stem cell populations isolated from extraocular and limb muscles

Eugenia C. Pacheco-Pinedo 1,2,*, Murat T. Budak 2,3,*, Ulrike Zeiger 1,2, Louise Helskov Jørgensen 4,5, Sasha Bogdanovich 1,2, Henrik Daa Schrøder 5, Neal A. Rubinstein 2,3 and Tejvir S. Khurana 1,2

1 Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania
2 Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, Pennsylvania
3 Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania
4 Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
5 Department of Clinical Pathology, University of Southern Denmark, Odense, Denmark

The extraocular muscles (EOMs) are a distinct muscle group that displays an array of unique contractile, structural, and regenerative properties. They also have differential sensitivity to certain diseases and are enigmatically spared in Duchenne muscular dystrophy (DMD). The EOMs are so distinct from other skeletal muscles that the term "allotype" has been coined to highlight EOM group-specific properties. We hypothesized that increased and distinct stem cells may underlie the continual myogenesis noted in EOM. The side population (SP) stem cells were isolated and studied. EOMs had 15x higher SP cell content compared with limb muscles. Expression profiling revealed 348 transcripts that define the EOM-SP transcriptome. Over 92% of transcripts were SP specific, because they were absent in previous whole muscle microarray studies. Cultured EOM-SP cells revealed superior in vitro proliferative capacity. Finally, assays of the committed progenitors or satellite cells performed on myofibers isolated from EOM and limb muscles independently validated the increased proliferative capacity of these muscles. We suggest a model in which unique EOM stem cells contribute to the continual myogenesis noted in EOM and consistent with a role for their sparing in DMD. We believe the greater numbers of stem cells, their unique transcriptome, the greater proliferative capacity of EOM stem cells, and the greater number of satellite cells also offer clues for novel cell-based therapeutic strategies.

side population; microarrays; Duchenne muscular dystrophy






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