Autocrine and paracrine angiopoietin 1/Tie-2 signaling promotes muscle satellite cell self-renewal

Cell Stem Cell. 2009 Sep 4;5(3):298-309. doi: 10.1016/j.stem.2009.06.001.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / metabolism*
  • Angiopoietin-1 / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Autocrine Communication* / drug effects
  • Cell Count
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Silencing / drug effects
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Muscle Development / drug effects
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • PAX7 Transcription Factor / metabolism
  • Paracrine Communication* / drug effects
  • Protein Binding / drug effects
  • Receptor, TIE-2 / metabolism*
  • Satellite Cells, Skeletal Muscle / cytology*
  • Satellite Cells, Skeletal Muscle / drug effects
  • Satellite Cells, Skeletal Muscle / enzymology
  • Satellite Cells, Skeletal Muscle / metabolism*
  • Signal Transduction* / drug effects
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism


  • Angiopoietin-1
  • PAX7 Transcription Factor
  • Receptor, TIE-2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3