Asymmetric self-renewal &commitment of satellite stem cells in muscle

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Cell. 2007 Jun 1;129(5):999-1010.

Asymmetric self-renewal and commitment of satellite stem cells in

muscle.

Kuang S, Kuroda K, Le Grand F, Rudnicki MA.

The Sprott Center for Stem Cell Research, Ottawa Health Research

Institute, Molecular Medicine Program, 501 Smyth Road, Ottawa, ON

K1H 8L6, Canada.

Satellite cells play a central role in mediating the growth and

regeneration of skeletal muscle. However, whether satellite cells

are stem cells, committed progenitors, or dedifferentiated myoblasts

has remained unclear.

Using Myf5-Cre and ROSA26-YFP Cre-reporter alleles, we observed that

in vivo 10% of sublaminar Pax7-expressing satellite cells have never

expressed Myf5. Moreover, we found that Pax7(+)/Myf5(-) satellite

cells gave rise to Pax7(+)/Myf5(+) satellite cells through apical-

basal oriented divisions that asymmetrically generated a basal Pax7

(+)/Myf5(-) and an apical Pax7(+)/Myf5(+) cells.

Prospective isolation and transplantation into muscle revealed that

whereas Pax7(+)/Myf5(+) cells exhibited precocious differentiation,

Pax7(+)/Myf5(-) cells extensively contributed to the satellite cell

reservoir throughout the injected muscle. Therefore, we conclude

that satellite cells are a heterogeneous population composed of stem

cells and committed progenitors.

These results provide critical insights into satellite cell biology

and open new avenues for therapeutic treatment of neuromuscular

diseases.