Wound infiltrating adipocytes are not myofibroblasts

Shruthi Kalgudde Gopal, Ruoxuan Dai, Ania Maria Stefanska, Meshal Ansari, Jiakuan Zhao, Pushkar Ramesh, Johannes W. Bagnoli, Donovan Correa-Gallegos, Yue Lin, Simon Christ, Ilias Angelidis, Valerio Lupperger, Carsten Marr, Lindsay C. Davies, Wolfgang Enard, Hans-Günther Machens, Herbert B. Schiller (), Dongsheng Jiang () and Yuval Rinkevich ()
Additional contact information
Shruthi Kalgudde Gopal: Helmholtz Center Munich
Ruoxuan Dai: Helmholtz Center Munich
Ania Maria Stefanska: Helmholtz Center Munich
Meshal Ansari: Helmholtz Center Munich
Jiakuan Zhao: Helmholtz Center Munich
Pushkar Ramesh: Helmholtz Center Munich
Johannes W. Bagnoli: Ludwig-Maximilian University Munich
Donovan Correa-Gallegos: Helmholtz Center Munich
Yue Lin: Helmholtz Center Munich
Simon Christ: Helmholtz Center Munich
Ilias Angelidis: Helmholtz Center Munich
Valerio Lupperger: Helmholtz Center Munich
Carsten Marr: Helmholtz Center Munich
Lindsay C. Davies: Tumour and Cell Biology (MTC), Karolinska Institute
Wolfgang Enard: Ludwig-Maximilian University Munich
Hans-Günther Machens: Technical University of Munich
Herbert B. Schiller: Helmholtz Center Munich
Dongsheng Jiang: Helmholtz Center Munich
Yuval Rinkevich: Helmholtz Center Munich

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract The origins of wound myofibroblasts and scar tissue remains unclear, but it is assumed to involve conversion of adipocytes into myofibroblasts. Here, we directly explore the potential plasticity of adipocytes and fibroblasts after skin injury. Using genetic lineage tracing and live imaging in explants and in wounded animals, we observe that injury induces a transient migratory state in adipocytes with vastly distinct cell migration patterns and behaviours from fibroblasts. Furthermore, migratory adipocytes, do not contribute to scar formation and remain non-fibrogenic in vitro, in vivo and upon transplantation into wounds in animals. Using single-cell and bulk transcriptomics we confirm that wound adipocytes do not convert into fibrogenic myofibroblasts. In summary, the injury-induced migratory adipocytes remain lineage-restricted and do not converge or reprogram into a fibrosing phenotype. These findings broadly impact basic and translational strategies in the regenerative medicine field, including clinical interventions for wound repair, diabetes, and fibrotic pathologies.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38591-6

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DOI: 10.1038/s41467-023-38591-6

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