Cell Stem Cell,5 June 2009 doi:10.1016/j.stem.2009.03.013

Wnt7a Activates the Planar Cell Polarity Pathway to Drive the Symmetric Expansion of Satellite Stem Cells

Fabien Le Grand1,2,3,Andrew E. Jones1,2,Vanessa Seale1,Anthony Scimè1,2andMichael A. Rudnicki1,2,,
1 Sprott Center for Stem Cell Research, Ottawa Hospital Research
Institute, Regenerative Medicine Program, 501 Smyth Road, Ottawa, ON
K1H 8L6, Canada
2 Department of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
3 Present address: Institut Cochin, INSERM U567, Université Paris Descartes, Paris 75014, France
Satellite cells in skeletal muscle are a heterogeneous population of
stem cells and committed progenitors. We found that quiescent satellite
stem cells expressed the Wnt receptor Fzd7 and that its candidate
ligand Wnt7a was upregulated during regeneration. Wnt7a markedly
stimulated the symmetric expansion of satellite stem cells but did not
affect the growth or differentiation of myoblasts. Silencing of Fzd7
abrogated Wnt7a binding and stimulation of stem cell expansion. Wnt7a
signaling induced the polarized distribution of the planar cell
polarity effector Vangl2. Silencing of Vangl2 inhibited Wnt7a action on
satellite stem cell expansion. Wnt7a overexpression enhanced muscle
regeneration and increased both satellite cell numbers and the
proportion of satellite stem cells. Muscle lacking Wnt7a exhibited a
marked decrease in satellite cell number following regeneration.
Therefore, Wnt7a signaling through the planar cell polarity pathway
controls the homeostatic level of satellite stem cells and hence
regulates the regenerative potential of muscle.

加拿大渥太華醫院研究所和渥太華大學的科學家找到了一種全新的刺激肌肉再生的有效方法，為找到一種新的治療諸如肌肉營養失調等肌肉衰弱病症的方法鋪平了道路。加科學家的研究首次表明，一種稱為Wnt7a的蛋白質可以提高肌肉組織中幹細胞的數量，進而可以加速骨骼肌的生長和修復。該項研究發表在6月5 日出版的《細胞—幹細胞》雜誌上。

幹細胞有助於人體組織和器官的生長。衛星幹細胞是特別的肌肉乾細胞，生活在成年人的骨骼肌肉組織中，具有複製和分化成各種不同類型肌肉細胞的雙重能力。加拿大干細胞研究網技術負責人，渥太華醫院研究所幹細胞研究中心主任，該項目主要研究人員邁克爾·魯德利基教授領導的研究小組發現，當Wnt7a蛋白質被引入實驗鼠肌肉組織中時，可以大大提高衛星幹細胞的數量，加速組織再生過程，生長出體積更大、力量更強壯的肌肉。實驗中，肌肉組織的質量增加了 20%。

魯德利基教授表示，該項發現表明，今後可以將研究目標集中於迅速增加幹細胞數量，以使身體提高修復肌肉組織的能力。他認為，該項發現為開發出全新的肌肉萎縮等肌肉類疾病治療方法指明了方向。