Paris, February 22, 2012

Two stem-cell subpopulations identified in skeletal muscles

In adults, specific stem cells are present within each organ: if necessary, they have the potential to completely regenerate the organ. But not all stem cells are alike. Researchers from the Institut Pasteur have recently detailed the existence of two populations of stem cells found in the skeletal muscles of mice. This discovery, recently published in the scientific journal Cell, opens new avenues for major advances in fundamental and therapeutic research and could potentially shed new light on cancer research.

Under normal circumstances our muscles are at rest, and skeletal muscle stem cells are referred to as “quiescent”. Following physical activity or trauma, however, these stem cells are stimulated into action to regenerate the damaged muscle tissue. But not all stem cells are created equal: two subpopulations of stem cells expressing the Pax7 marker have recently been characterized in the skeletal muscles of mice. Pax7-low stem cells (named for their low level of the Pax7 protein) divide to produce skeletal muscle daughter cells for muscle repair and Pax7-high stem cells (named for their high level of the Pax7 protein) divide to produce both stem cells and differentiated muscle cells.

The division process for Pax7-high stem cells is referred to as “asymmetric” because each cell divides to produce two distinct daughter cells. This ensures that a viable level of stem cells is retained while also repairing the damaged muscle. The DNA within these cells also undergoes asymmetrical division, meaning that the older DNA strands from the original stem cell go to the daughter stem cell and that the newer copied DNA strands go to the daughter skeletal muscle cell that differentiates.

“The identification of these two stem cell subpopulations that show distinct behaviours when faced with trauma to skeletal muscle, is an important step forward", explains head of the Stem Cells and Development Unit at the Institut Pasteur, Professor Shahragim Tajbakhsh. “Our understanding of the role these stem cells play as well as their associated mechanisms is constantly growing and could have a considerable impact on fundamental research as well as on future innovative therapies”.

Researchers do not yet understand why some stem cells divide asymmetrically while others divide symmetrically but, it does seem that the former process of cell division maintains a population of stem cells in which the original DNA strands are conserved. Two theories can therefore be considered, that this mechanism is meant to protect against potential errors during DNA replication, or that a specific message linked to the original DNA plays a role in deciding the outcome of daughter cells.

In other studies, researchers have also shown that genes that play a predominant role in asymmetric division are also often tumor-suppressor genes. This convergence of research on stem cell and cancer cell biology has generated considerable interest in identifying "cancerous" stem cells to explain why some tumours reappear even after extensive treatments. These observations have already opened up exciting research possibilities.

In closing, the characterization of these two stem cell subpopulations in skeletal muscle could prove foundational in the development of potential applications in biomedical research. Because Pax7 has been identified as a marker that distinguishes these two populations, scientists can now isolate them to obtain homogenous cultures. These cultures will be indispensible in the study of information retained with the original DNA strands in asymmetric division as well as in revealing how these DNA strands are selected during cell division and how this process relates to the different identities of the daughter cells.



 A subpopulation of adult muscle stem cells retains all template DNA strands after cell division – Cell – January, 19, 2012

Pierre Rocheteau1, Barbara Gayraud-Morel1, Irene Siegl-Cachedenier 2*, Maria Blasco2, and Shahragim Tajbakhsh1*

(1) Institut Pasteur, Stem Cells & Development, 2CNRS URA 2578, 25 rue du Dr. Roux, Paris, F-75015, France;
(2) Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro, 3, 28029 Madrid, Spain



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