Fibroblast growth factor signaling induces a chondrocyte-like state of peripheral nerve fibroblast during aging
During aging, peripheral nerves undergo structural and cellular changes that trigger loss of function, impair quality of life, and increase disease risk. During peripheral nerve aging there are cellular and molecular changes, such as increased extracellular matrix deposition. The mechanisms behind these aging-induced alterations remain unclear. Here, we profile mouse sciatic nerves using single nucleus transcriptomics and unravel changes in macrophage subtypes during nerve aging. Phagocytic macrophage numbers increase at the onset of aging, followed by higher numbers of chronic inflammatory macrophages. Based on ligand-receptor analysis, we predict that increased fibroblast growth factor (FGF) signaling from adipocytes activates a chondrocyte-like neural fibroblast state during peripheral nerve aging. Finally, we show that FGF2 induces the co-expression of the chondrocyte markers SOX9 and FOXC2 in senescent human perineurial fibroblast, that can be blocked with FGF1. In conclusion, our findings reveal some of the molecular mechanisms of peripheral nerve aging by FGF-regulated induction of a chondrocyte-like fibroblast state.
Authors
- Dragana Stefanovska (ORCID: https://orcid.org/0009-0008-1315-1605)
- Björn Grüning (ORCID: https://orcid.org/0000-0002-3079-6586)
- Sebastian Preißl (ORCID: https://orcid.org/0000-0001-8971-5616)
- Madelon Hoßfeld (ORCID: https://orcid.org/0009-0008-1574-9475)
- Sebastian J. Arnold (ORCID: https://orcid.org/0000-0002-2688-9210)
- Marco Prinz (ORCID: https://orcid.org/0000-0002-0349-1955)
- Franziska Schneider‐Warme (ORCID: https://orcid.org/0000-0002-5873-9436)
- Amirhossein Naghsh Nilchi (ORCID: https://orcid.org/0000-0003-1329-3044)
- Lauritz Miarka (ORCID: https://orcid.org/0009-0009-2998-8503)
- Mehmet Tekman (ORCID: https://orcid.org/0000-0002-4181-2676)
- Eliza Sassu (ORCID: https://orcid.org/0009-0006-2898-5819)
- Stefanie Perez‐Feliz (ORCID: https://orcid.org/0009-0009-2880-2367)
- Syed G. Haider (ORCID: https://orcid.org/0009-0006-1727-7681)
- Claudia Domisch
- Luis Hortells (ORCID: https://orcid.org/0000-0001-6155-8612)
Institutions
- University of Graz (AT)
- University of Freiburg (DE)
- Bernstein Center for Computational Neuroscience Freiburg (DE)
- Universitäts-Herzzentrum Freiburg-Bad Krozingen (DE)
- UiT The Arctic University of Norway (NO)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1038/s41467-025-65297-8
- Primary Topic
- Nerve injury and regeneration
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Universitetet i Tromsø
- Deutsche Forschungsgemeinschaft
- Albert-Ludwigs-Universität Freiburg
- Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg