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=500), 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.
from sddb import Catalog
cohort = Catalog().collection("geo-gse277435")
cohort.members # the 12 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse277435")
coll.ordered_artifacts.to_dataframe() # the 12 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse277435 --dest data/Licenses: 12 NCBI GEO policy
@article{Fagiani_2025,
title = {Spatially-restricted inflammation-induced senescent-like glia in multiple sclerosis and patient-derived organoids},
volume = {16},
ISSN = {2041-1723},
url = {http://dx.doi.org/10.1038/s41467-025-63371-9},
DOI = {10.1038/s41467-025-63371-9},
number = {1},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
author = {Fagiani, Francesca and Pedrini, Edoardo and Martire, Maria Sofia and Gastoldi, Gaia and Vanden Bulcke, Colin and Lin, Jing-Ping and Maric, Dragan and Brambilla, Elena and Ruffini, Francesca and Peri, Carolina and Calabresi, Peter A. and Maggi, Pietro and Panina-Bordignon, Paola and Martino, Gianvito and Reich, Daniel S. and Absinta, Martina},
year = {2025},
month = Sept
}