IGF-I Concentration Determines Cell Fate by Converting Signaling Dynamics As a Bifurcation Parameter in L6 Myoblasts

Overview

Journal Sci Rep

Specialty Science

Date 2024 Sep 5

PMID 39237579

Authors

Ryosuke Okino

Kazuaki Mukai

Shunpei Oguri

Masato Masuda

Satoshi Watanabe

Yosuke Yoneyama

Sumine Nagaosa

Takafumi Miyamoto

Atsushi Mochizuki

Shin-Ichiro Takahashi

Fumihiko Hakuno

Affiliations

Soon will be listed here.

Abstract

Insulin-like growth factor (IGF)-I mediates long-term activities that determine cell fate, including cell proliferation and differentiation. This study aimed to characterize the mechanisms by which IGF-I determines cell fate from the aspect of IGF-I signaling dynamics. In L6 myoblasts, myogenic differentiation proceeded under low IGF-I levels, whereas proliferation was enhanced under high levels. Mathematical and experimental analyses revealed that IGF-I signaling oscillated at low IGF-I levels but remained constant at high levels, suggesting that differences in IGF-I signaling dynamics determine cell fate. We previously reported that differential insulin receptor substrate (IRS)-1 levels generate a driving force for cell competition. Computational simulations and immunofluorescence analyses revealed that asynchronous IRS-1 protein oscillations were synchronized during myogenic processes through cell competition. Disturbances of cell competition impaired signaling synchronization and cell fusion, indicating that synchronization of IGF-I signaling oscillation is critical for myoblast cell fusion to form multinucleate myotubes.

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