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This Article Full Text Full Text (PDF) All Versions of this Article: jas.2007-0473v1 86/14_suppl/E207    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yablonka-Reuveni, Z. Articles by Shefer, G. PubMed PubMed Citation Articles by Yablonka-Reuveni, Z. Articles by Shefer, G.

Defining the transcriptional signature of skeletal muscle stem cells^1,2

Z. Yablonka-Reuveni^*, K. Day^3,*, A. Vine^* and G. Shefer

^* Department of Biological Structure, University of Washington School of Medicine, Seattle 98195; and and Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel

³ Corresponding author: reuveni{at}u.washington.edu

Satellite cells, the main source of myoblasts in postnatal muscle, are located beneath the myofiber basal lamina. The myogenic potential of satellite cells was initially documented based on their capacity to produce progeny that fused into myotubes. More recently, molecular markers of resident satellite cells were identified, further contributing to defining these cells as myogenic stem cells that produce differentiating progeny and self-renew. Herein, we discuss aspects of the satellite cell transcriptional milieu that have been intensively investigated in our research. We elaborate on the expression patterns of the paired box (Pax) transcription factors Pax3 and Pax7, and on the myogenic regulatory factors myogenic factor 5 (Myf5), myogenic determination factor 1 (MyoD), and myogenin. We also introduce original data on MyoD upregulation in newly activated satellite cells, which precedes the first round of cell proliferation. Such MyoD upregulation occurred even when parent myofibers with their associated satellite cells were exposed to pharmacological inhibitors of hepatocyte growth factor and fibroblast growth factor receptors, which are typically involved in promoting satellite cell proliferation. These observations support the hypothesis that most satellite cells in adult muscle are committed to rapidly entering myogenesis. We also detected expression of serum response factor in resident satellite cells prior to MyoD expression, which may facilitate the rapid upregulation of MyoD. Aspects of satellite cell self-renewal based on the reemergence of cells expressing Pax7, but not MyoD, in myogenic cultures are discussed further herein. We conclude by describing our recent studies using transgenic mice in which satellite cells are traced and isolated based on their expression of green fluorescence protein driven by regulatory elements of the nestin promoter (nestin-green fluorescence protein). This feature provides us with a novel means of studying satellite cell transcriptional signatures, heterogeneity among muscle groups, and the role of the myogenic niche in directing satellite cell self-renewal.

Key Words: Myf5 • MyoD • Pax7 • satellite cell • Sox • SRF