Autocrine and Paracrine Angiopoietin 1/Tie-2 Signaling Promotes Muscle Satellite Cell Self-Renewal

Abstract

SUMMARY 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) up-regulated 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.

Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin

“…After 48 or 72 h of treatment, floating fibers were fixed in 4% (wt/vol) PFA, rinsed in PBS, and immediately used for immunostaining. Primary antibodies used are as follows: MyoD (1:50; Dako or Santa Cruz Biotechnology), Pax7 [1:10; Developmental Studies Hybridoma Bank (DSHB)] (26), β-gal (1:350; Biogenesis), and Ki67 (1:250; Abcam) (53).…”

Cell death, clearance and immunity in the skeletal muscle

“…A fraction of proliferating satellite cells die, as assessed by positivity of the TUNEL assay and by the cleavage of poly ADP ribose polymerase, via a pathway involving the Foxo3 transcription factor. 51 Specific pathways have apparently been generated to modulate the ability of satellite cells to survive in response to various environmental stimuli including those related to the angiopoietin 1/Tie2 system, 52 to the member of the Melanomaassociated antigen D1 family of proteins, necdin, 53 and to the thyroid hormone. 51 FAPs comprise multipotent mesenchymal progenitor cells 54 that are a source of matrix-secreting activated myofibroblasts in the skeletal muscle.…”

Les cellules du muscle chantent en chœur une berceuse pour cellules souches

“…Rôle du couple Ang1/Tie-2 dans la régulation du cycle cellulaire des progéniteurs musculaires et la constitution de cellules de réserve Nous avons exploré le rôle du système Ang1/Tie-2 dans la régulation du destin des précurseurs myogéniques, in vitro dans un système de culture de cellules humaines, et in vivo dans des modèles murins [11]. L'expression de Ang1 et de son récepteur Tie-2 est particulièrement forte dans les cellules de réserve.…”

“…Enfin, des expériences in vivo de gain et perte de fonction ont été réalisées [11]. Dans un muscle en phase de régé-nération après une lésion, l'expression de Tie-2 a été inhibée par des anticorps bloquants alors que Ang1 a été surexprimée après électroporation.…”