Submitted on March 11, 2008
Accepted on December 23, 2008
Transcriptional and functional differences in stem cell populations isolated from Extraocular and Limb muscles
Eugenia Cristina Pacheco-Pinedo1, Murat T. Budak2, Ulrike Zeiger1, Louise Helskov Jorgensen3, Sasha Bogdanovich1, Henrik Daa Schroeder4, Neal A. Rubinstein2, and Tejvir S Khurana1*
1 Physiology - Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States
2 Cell & Developmental Biology - Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States
3 Institute of Clinical Research - Department of Clinical Pathology, University of Southern Denmark, Odense, Denmark
4 Department of Clinical Pathology, University of Southern Denmark, Odense, Denmark
* To whom correspondence should be addressed. E-mail: tsk{at}mail.med.upenn.edu.
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 to limb muscles. Expression profiling revealed 348 transcripts that define the EOM-SP transcriptome. Over 92% of transcripts were SP-specific, as 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 increased proliferative capacity of these muscles. We suggest a model wherein unique EOM stem cells contribute to the continual myogenesis noted in EOM and is 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 greater number of satellite cells also offers clues for novel cell-based therapeutic strategies.
