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Skeletal Muscle Tissue Damage Leads to a Conserved Stress Response and Stem Cell-Specific Adaptive Transitions

48 Pages Posted: 18 Feb 2020 Publication Status: Published

See all articles by Léo Machado

Léo Machado

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Matthieu Dos Santos

Institut Cochin

Jordi Camps

KU Leuven - Laboratory of Translational Cardiomyology

Jens Van Herck

KU Leuven - Laboratory of Reproductive Genomics

Hugo Varet

Institut Pasteur - Hub de Bioinformatique et Biostatistique

Rachel Legendre

Institut Pasteur - Hub de Bioinformatique et Biostatistique

Maurilio Sampaolesi

KU Leuven - Laboratory of Translational Cardiomyology

Thierry Voet

KU Leuven - Laboratory of Reproductive Genomics

Pascal Maire

Universite Paris Descartes - Institut Cochin; University of Angers - French Institute of Health and Medical Research (INSERM)

Frederic Relaix

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

Philippos Mourikis

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB)

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Abstract

Every cell in a multicellular organism is dynamically interacting with its microenvironment, which determine its properties and gene-expression profile. Tissue damage, such as injury or experimental cell dissociation, leads to dramatic modifications of the microenvironment, yet the cell-type specific transcriptional responses to the stress-induced stimuli remain ill-defined. In order to identify the early events linked with tissue damage, we generated single-nucleus atlases from intact, dissociated or injured muscle and liver, and identified a common early stress response and cell-type specific transcriptional modifications. This prevalent stress response was also detected in other organs at varying levels across cell types and tissues in published datasets, demonstrating high conservation but also indicating a significant degree of data distortion in single-cell reference atlases. Skeletal muscle stem cells are mitotically quiescent during adult homeostasis and get activated in response to acute muscle damage. To further investigate the muscle stem cell-specific response to activation, we performed time course analysis, revealing that the conserved stress response is distinct and precedes the initiation of the myogenic program. Our study therefore defines the initial events governing stem cell activation in response to perturbations in tissue integrity in vivo, and identifies a broadly conserved stress response that acts in parallel to cell-specific adaptive alterations.

Keywords: muscle stem cells, quiescence, single-cell RNA-seq, single-cell atlases, stress response

Suggested Citation

Machado, Léo and Dos Santos, Matthieu and Camps, Jordi and Van Herck, Jens and Varet, Hugo and Legendre, Rachel and Sampaolesi, Maurilio and Voet, Thierry and Maire, Pascal and Relaix, Frederic and Mourikis, Philippos, Skeletal Muscle Tissue Damage Leads to a Conserved Stress Response and Stem Cell-Specific Adaptive Transitions. Available at SSRN: https://ssrn.com/abstract=3537798 or http://dx.doi.org/10.2139/ssrn.3537798
This version of the paper has not been formally peer reviewed.

Léo Machado

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB) ( email )

France

Matthieu Dos Santos

Institut Cochin ( email )

France

Jordi Camps

KU Leuven - Laboratory of Translational Cardiomyology ( email )

Belgium

Jens Van Herck

KU Leuven - Laboratory of Reproductive Genomics ( email )

Belgium

Hugo Varet

Institut Pasteur - Hub de Bioinformatique et Biostatistique ( email )

France

Rachel Legendre

Institut Pasteur - Hub de Bioinformatique et Biostatistique ( email )

France

Maurilio Sampaolesi

KU Leuven - Laboratory of Translational Cardiomyology ( email )

Belgium

Thierry Voet

KU Leuven - Laboratory of Reproductive Genomics ( email )

Belgium

Pascal Maire

Universite Paris Descartes - Institut Cochin

France

University of Angers - French Institute of Health and Medical Research (INSERM)

101 rue de Tolbiac
75654 Paris Cedex 13
France

Frederic Relaix (Contact Author)

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB) ( email )

France

Philippos Mourikis

French National Institute of Health and Medical Research (INSERM) - Mondor Biomedical Research Institute (IMRB) ( email )

France

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