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Research Paper|Volume 14, Issue 9|pp 3728—3756

Single-cell transcriptomics reveals age-resistant maintenance of cell identities, stem cell compartments and differentiation trajectories in long-lived naked mole-rats skin

Aleksandra Savina1, Thierry Jaffredo2, Frederic Saldmann3, Chris G. Faulkes4, Philippe Moguelet5, Christine Leroy6, Delphine Del Marmol7, Patrice Codogno6, Lucy Foucher8, Antoine Zalc1, Mélanie Viltard3, Gérard Friedlander6, Selim Aractingi1,9, Romain H. Fontaine1
  • 1Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
  • 2Institut de Biologie Paris Seine (IBPS), Laboratoire de Biologie du Développement, Sorbonne Université, CNRS, INSERM, Paris, France
  • 3Fondation pour la Recherche en Physiologie, Brussels, Belgium
  • 4Queen Mary University of London, School of Biological and Chemical Sciences, London, United Kingdom
  • 5Service d'Anatomie et Cytologie Pathologiques, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France
  • 6Université Paris Cité, CNRS, INSERM, Institut Necker-Enfants Malades, Paris, France
  • 7Université de Namur ASBL, Namur, Belgium
  • 8Ecole Nationale Vétérinaire d'Alfort, Centre de Recherche Biomédicale, Maisons-Alfort, France
  • 9Service de Dermatologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, France
* Senior co-author
Received: December 1, 2021Accepted: April 25, 2022Published: May 4, 2022
https://doi.org/10.18632/aging.204054

Copyright: © 2022 Savina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Naked mole-rats (NMR) are subterranean rodents characterized by an unusual longevity coupled with an unexplained resistance to aging. In the present study, we performed extensive in situ analysis and single-cell RNA-sequencing comparing young and older animals. At variance with other species, NMR exhibited a striking stability of skin compartments and cell types, which remained stable over time without aging-associated changes. Remarkably, the number of stem cells was constant throughout aging. We found three classical cellular states defining a unique keratinocyte differentiation trajectory that were not altered after pseudo-temporal reconstruction. Epidermal gene expression did not change with aging either. Langerhans cell clusters were conserved, and only a higher basal stem cell expression of Igfbp3 was found in aged animals. In accordance, NMR skin healing closure was similar in young and older animals. Altogether, these results indicate that NMR skin is characterized by peculiar genetic and cellular features, different from those previously demonstrated for mice and humans. The remarkable stability of the aging NMR skin transcriptome likely reflects unaltered homeostasis and resilience.