西亚试剂：Wnt7a Activates the Planar Cell Polarity Pathway to Drive t

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.

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