Autocrine and paracrine angiopoietin 1/Tie-2 signaling promotes muscle satellite cell self-renewal.
Mechanisms governing muscle satellite cell withdrawal from cell cycle to enter into quiescence remain poorly understood. We studied the role of angiopoietin 1 (Ang1) and its receptor Tie-2 in the regulation of myogenic precursor cell (mpc) fate. In human and mouse, Tie-2 was preferentially expressed by quiescent satellite cells in vivo and reserve cells (RCs) in vitro. Ang1/Tie-2 signaling, through ERK1/2 pathway, decreased mpc proliferation and differentiation, increased the number of cells in G0, increased expression of RC-associated markers (p130, Pax7, Myf-5, M-cadherin), and downregulated expression of differentiation-associated markers. Silencing Tie-2 had opposite effects. Cells located in the satellite cell neighborhood (smooth muscle cells, fibroblasts) upregulated RC-associated markers by secreting Ang1 in vitro. In vivo, Tie-2 blockade and Ang1 overexpression increased the number of cycling and quiescent satellite cells, respectively. We propose that Ang1/Tie-2 signaling regulates mpc self-renewal by controlling the return to quiescence of a subset of satellite cells.
Abou-Khalil
Rana
R
INSERM, U955, Créteil, France.
Le Grand
Fabien
F
Pallafacchina
Giorgia
G
Valable
Samuel
S
Authier
François-Jérôme
FJ
Rudnicki
Michael A
MA
Gherardi
Romain K
RK
Germain
Stéphane
S
Chretien
Fabrice
F
Sotiropoulos
Athanassia
A
Lafuste
Peggy
P
Montarras
Didier
D
Chazaud
Bénédicte
B
D042683:Angiopoietin-1 / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D024510:Muscle Development / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D042787:Receptor, TIE-2 / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D042683:Angiopoietin-1; D051763:PAX7 Transcription Factor; D042787:Receptor, TIE-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3