Role of autophagy in muscle stem cell differentiation

• Grant number: 19/15428-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): November 29, 2019
• Effective date (End): November 28, 2020
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Ana Paula Pinto
• Supervisor: Joe Quadrilatero
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: University of Waterloo, Canada
• Associated to the scholarship: 17/19869-8 - Molecular mechanisms related to increased hepatic fat content in response to excessive physical exercise, BP.DR

Abstract

The satellite cells (SCS) or skeletal muscle steam cells are responsible for growth and regeneration of muscle fibers. The SCs are located between the basement membrane and the sarcolemma in muscle fibers. Several signaling pathways regulate SCs proliferation and differentiation. It has been demonstrated that autophagy is involved in the proper function and maintenance of stem cells populations through promoting their quiescence, as well as maintaining their stemness and self-renewal properties. Autophagy degrades macromolecules and organelles which results on recycling of the bioenergetics components. Autophagy has a fundamental cellular role such as cellular growing and development, organelles biogenesis and regulating the balance between protein synthesis and degradation. Mouse with Atg7-deficient muscle has a decrease in the satellite cell numbers. Interestingly, the autophagy deficiency leads to a very similar phenotype as that observed in aged satellite cells, including DNA damage, oxidative stress, accumulation of SQSTM1 protein, damaged mitochondria, and senescence markers. Given this, we hypothesize that autophagy could act in a similar manner in skeletal muscle to allow muscle differentiation to occur while also preventing SC depletion. The main objective of the study will be determining if autophagy-deficient SCs efficiently undergo myogenesis in vitro and if autophagy-deficient cells can effectively regenerate skeletal muscle in vivo.