Single cell landscape of sex differences in the different courses of multiple sclerosis
5 affiliations
- 1Computational Biomedicine Laboratory, Principe Felipe Research Center (CIPF)
- 2Research Group in Immunotherapy and Biomodels for Autoimmunity, Instituto de Investigación Sanitaria La Fe
- 3Neurobiology Unit, Program in Neuroscience Institute of Biotechnology and Biomedicine (BIOTECMED), Universidad de Valencia
- 4Joint Unit in Biomedical Imaging FISABIO-CIPF, Foundation for the Promotion of Health and Biomedical Research of Valencia Region
- 5Laboratory of Comparative and Regenerative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia
Abstract
Background One of the major challenges in addressing multiple sclerosis is to understand its progression trajectory. The pathological process transitions from acute phases predominantly driven by inflammation to progressive clinical profiles where neurodegeneration takes precedence. It is known that sex plays a crucial role in this heterogeneity; females are two to three times more likely to suffer from multiple sclerosis, while males suffer from more rapid neurodegeneration with greater severity. Results To gain insight into the sex-based molecular differences, we processed single cell datasets from the central nervous system and the peripheral blood, covering the different courses of multiple sclerosis. We generated cell-type specific landscapes, including gene signatures from differentially expressed genes, functional profiling, pathway activation, and cell-cell communication networks for females, males, and their sex differential profiles. Among our findings, we revealed that female neurons may exhibit protective mechanisms against neurodegeneration. In the inflammatory-predominant forms, female immune cells present an inflammatory core driven by the AP-1 transcription factor, while male adaptive immune cells exhibit higher mitochondrial impairment. Conversely, larger differences are reported in CD8 + T cells progressive forms, with males exhibiting cytolytic profiles that may promote neurodegeneration. Complete results can be explored in the interactive webtool https://irsoler.shinyapps.io/cbl-atlas-ms/ . Conclusions We identified cell-type specific sex differences in brain and immune cells that vary in the spectrum of multiple sclerosis. We consider this molecular description a valuable resource to promote future targeted approaches considering the sex of the individual.
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BibTeX
@article{solersaez2026single,
title = {{Single cell landscape of sex differences in the different courses of multiple sclerosis}},
author = {Irene Soler-Sáez and Borja Gómez-Cabañes and Rubén Grillo-Risco and Cristina Galiana-Roselló and Lucas Barea-Moya and Héctor Carceller and María de la Iglesia-Vayá and Sara Gil-Perotin and Vanja Tepavčević and Marta R. Hidalgo and Francisco García-García},
journal = {Biology of Sex Differences},
year = {2026},
month = jul,
doi = {10.1186/s13293-026-00957-y},
url = {https://doi.org/10.1186/s13293-026-00957-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single cell landscape of sex differences in the different courses of multiple sclerosis
AU - Irene Soler-Sáez
AU - Borja Gómez-Cabañes
AU - Rubén Grillo-Risco
AU - Cristina Galiana-Roselló
AU - Lucas Barea-Moya
AU - Héctor Carceller
AU - María de la Iglesia-Vayá
AU - Sara Gil-Perotin
AU - Vanja Tepavčević
AU - Marta R. Hidalgo
AU - Francisco García-García
PY - 2026
DA - 2026/07/01
JO - Biology of Sex Differences
DO - 10.1186/s13293-026-00957-y
UR - https://doi.org/10.1186/s13293-026-00957-y
AB - Background One of the major challenges in addressing multiple sclerosis is to understand its progression trajectory. The pathological process transitions from acute phases predominantly driven by inflammation to progressive clinical profiles where neurodegeneration takes precedence. It is known that sex plays a crucial role in this heterogeneity; females are two to three times more likely to suffer from multiple sclerosis, while males suffer from more rapid neurodegeneration with greater severity. Results To gain insight into the sex-based molecular differences, we processed single cell datasets from the central nervous system and the peripheral blood, covering the different courses of multiple sclerosis. We generated cell-type specific landscapes, including gene signatures from differentially expressed genes, functional profiling, pathway activation, and cell-cell communication networks for females, males, and their sex differential profiles. Among our findings, we revealed that female neurons may exhibit protective mechanisms against neurodegeneration. In the inflammatory-predominant forms, female immune cells present an inflammatory core driven by the AP-1 transcription factor, while male adaptive immune cells exhibit higher mitochondrial impairment. Conversely, larger differences are reported in CD8 + T cells progressive forms, with males exhibiting cytolytic profiles that may promote neurodegeneration. Complete results can be explored in the interactive webtool https://irsoler.shinyapps.io/cbl-atlas-ms/ . Conclusions We identified cell-type specific sex differences in brain and immune cells that vary in the spectrum of multiple sclerosis. We consider this molecular description a valuable resource to promote future targeted approaches considering the sex of the individual.
SN - 2042-6410
ER -