| Title: |
Spatially-restricted inflammation-induced senescent-like glia in multiple sclerosis and patient-derived organoids |
| Authors: |
Fagiani, F.; Pedrini, E.; Martire, M.S.; Gastoldi, G.; Vanden Bulcke, Colin; Lin, J.-P.; Maric, D.; Brambilla, E.; Ruffini, F.; Peri, C.; Calabresi, P.A.; Maggi, Pietro; Panina-Bordignon, P.; Martino, G.; Reich, D.S.; Absinta, M. |
| Contributors: |
UCL - SSS/IONS/NEUR - Clinical Neuroscience |
| Source: |
Nature Communications, Vol. 16, no.1, p. 8477 (2025) |
| Publication Year: |
2025 |
| Collection: |
DIAL@USL-B (Université Saint-Louis, Bruxelles) |
| Description: |
In multiple sclerosis (MS), chronic compartmentalized inflammation is thought to drive relentless clinical deterioration. Here, we investigate the link between unresolved parenchymal inflammation and cellular senescence in MS progression. Single-cell transcriptomic analysis of human brain tissue reveals an accumulation of senescent-like glial cells in diseased white matter, especially in chronic active lesions, and to a lesser extent in the cortex. Spatial transcriptomics show gradients of senescence-like signatures extending from lesion cores to periplaque regions, alongside rewired cellular networks. Experimental induction of senescence in MS hiPSC-derived neural organoids demonstrates that microglia are especially vulnerable to inflammation-induced senescence, which can be partially rescued by CNS-penetrant anti-inflammatory drugs. At the patient level (n = 466), increased 3T MRI-estimated brain-age is observed, especially in individuals with more than four chronic active lesions. These findings suggest that chronic inflammation might accelerate senescence-like processes, potentially contributing to disease progression, and that its modulation might help limit further propagation. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
boreal:306374; https://hdl.handle.net/2078.1/306374 |
| DOI: |
10.1038/s41467-025-63371-9 |
| Availability: |
https://hdl.handle.net/2078.1/306374; https://doi.org/10.1038/s41467-025-63371-9 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.EB610AE0 |
| Database: |
BASE |