The immune landscape of murine skeletal muscle regeneration and aging
Neuza S. Sousa,
Marta Bica,
Margarida F. Brás,
Ana C. Sousa,
Inês B. Antunes,
Isabel A. Encarnação,
Tiago M. Costa,
Inês B. Martins,
Nuno L. Barbosa-Morais,
Pedro Sousa-Victor,
Joana Neves
Affiliations
Neuza S. Sousa
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal; Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
Marta Bica
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal; Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
Margarida F. Brás
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal
Ana C. Sousa
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal
Inês B. Antunes
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal
Isabel A. Encarnação
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal
Tiago M. Costa
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal; Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
Inês B. Martins
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal; Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
Nuno L. Barbosa-Morais
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal
Pedro Sousa-Victor
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal; Corresponding author
Joana Neves
GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal; Corresponding author
Summary: Age-related alterations in the immune system are starting to emerge as key contributors to impairments found in aged organs. A decline in regenerative capacity is a hallmark of tissue aging; however, the contribution of immune aging to regenerative failure is just starting to be explored. Here, we apply a strategy combining single-cell RNA sequencing with flow cytometry, histological analysis, and functional assays to perform a complete analysis of the immune environment of the aged regenerating skeletal muscle on a time course following injury with single-cell resolution. Our results reveal an unanticipated complexity and functional heterogeneity in immune populations within the skeletal muscle that have been regarded as homogeneous. Furthermore, we uncover a profound remodeling of both myeloid and lymphoid compartments in aging. These discoveries challenge established notions on immune regulation of skeletal muscle regeneration, providing a set of potential targets to improve skeletal muscle health and regenerative capacity in aging.
