Tissue damage induces a conserved stress response that initiates quiescent muscle stem cell activation
Open accessAbstract
Tissue damage dramatically alters how cells interact with their microenvironment. These changes in turn dictate cellular responses, such as stem cell activation, yet early cellular responses in vivo remain ill defined. We generated single-cell and nucleus atlases from intact, dissociated, and injured muscle and liver and identified a common stress response signature shared by multiple cell types across these organs. This prevalent stress response was detected in published datasets across a range of tissues, demonstrating high conservation but also a significant degree of data distortion in single-cell reference atlases. Using quiescent muscle stem cells as a paradigm of cell activation following injury, we captured early cell activation following muscle injury and found that an essential ERK1/2 primary proliferation signal precedes initiation of the Notch-regulated myogenic program. This study defines initial events in response to tissue perturbation and identifies a broadly conserved transcriptional stress response that acts in parallel with cell-specific adaptive alterations.
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Emerging results from other tissues and cell types have begun to characterize dissociation artifacts following enzymatic digestion.
“However, emerging results from other tissues/cell types have begun to characterize dissociation artifacts following enzymatic digestion43–45,65,66.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [66]
To evaluate the effects of liver dissociation on scRNA-Seq datasets, AddModuleScore function was used to assess module scores of stress response genes in hepatocytes.
“To evaluate the effects of liver dissociation to our scRNA-Seq datasets, AddModuleScore function was used to assess the module scores of stress response genes in hepatocytes.17”
From Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers (2023) · cites this paper as [17]
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- Authors
- Machado, L., Geara, P., Camps, J., Dos Santos, M., Teixeira-Clerc, F., Van Herck, J., Varet, H., Legendre, R., Pawlotsky, J.-M., Sampaolesi, M., Voet, T., Maire, P., Relaix, F., & Mourikis, P.
- Affiliations
- Inserm (FR)
- KU Leuven (BE)
- Centre National de la Recherche Scientifique (FR)
- University of Pavia (IT)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Mourikis, Philippos
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 28
- Issue
- 6
- Pages
- 1125-1135.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W3130604533
- Cited by
- 170
- References
- 60
- Citations by year
- 2026: 33 · 2025: 28 · 2024: 40 · 2023: 29 · 2022: 24 · 2021: 14 · 2020: 1
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion, cc-by-nc)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- KU Leuven (C14/18/092)
- Fonds Wetenschappelijk Onderzoek (G092415N, I001818N)
- Association Française contre les Myopathies
- Agence Nationale de la Recherche (ANR-17-CE14-0018-01, ANR-16-CE14-0002-03, ANR-19-CE13-0010, ANR-13-BSV1-0011-02, ANR-15-RHUS-0003, ANR-15-CE13-0011-01, ANR-10-LABX-73)
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- AFM-Téléthon (22946)
- Fondation pour la Recherche Médicale (ECO201806006793)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- tissue damage, stress response, muscle stem cells, muscle damage, liver injury, ERK signaling, Notch signaling, myogenesis, transcriptional stress response, cell microenvironment
- MeSH terms
- Muscles, Stem Cells, Muscle Development, Satellite Cells, Skeletal Muscle, Cell Proliferation
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