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@ARTICLE{delaRosa:285047,
author = {de la Rosa, Clara and Kendirli, Arek and Baygün, Seren and
Bauernschmitt, Franz and Thomann, Anna S and Kisioglu, Ilgin
and Beckmann, Daniela and Carpentier Solorio, Yves and
Pfaffenstaller, Veronika and Tai, Yi-Heng and Mehraein, Niel
and Sanchez, Paula and Spieth, Lena and Gerdes, Lisa Ann and
Beltran, Eduardo and Dornmair, Klaus and Simons, Mikael and
Peters, Anneli and Schmidt-Supprian, Marc and
Kerschensteiner, Martin},
title = {{I}n vivo {CRISPR} screen reveals regulation of macrophage
states in neuroinflammation.},
journal = {Nature neuroscience},
volume = {29},
number = {2},
issn = {1097-6256},
address = {New York, NY},
publisher = {Nature America},
reportid = {DZNE-2026-00171},
pages = {493 - 509},
year = {2026},
abstract = {Here we established an in vivo CRISPR screening pipeline
using genetically editable progenitor cells to dissect
macrophage regulation in mouse models of multiple sclerosis
(MS). Screening over 100 cytokine receptors and signaling
molecules identified interferon-γ, tumor necrosis factor,
granulocyte-macrophage colony-stimulating factor and
transforming growth factor-β as essential regulators of
macrophage polarization in vivo. Single-cell transcriptomics
confirmed that transferred progenitor cells generate all
blood-derived CNS myeloid cell populations, enabling
Perturb-seq analysis of cytokine actions in
neuroinflammation. Combined with biosensor expression, our
approach allows monitoring cytokine effects on myeloid cell
migration, debris phagocytosis and oxidative activity in
vivo. Comparative transcriptomic analyses revealed conserved
neuroinflammatory cytokine signatures across myeloid
populations, CNS compartments and species, elucidating
cytokine cues shaping myeloid function in the cerebrospinal
fluid and parenchyma of individuals with MS. This versatile
pipeline thus provides a scalable framework for
high-resolution analysis of macrophage states and uncovers
the cytokine signals that underlie their regulation in MS
and MS models.},
keywords = {Animals / Macrophages: metabolism / Mice / Cytokines:
metabolism / Cytokines: genetics / Mice, Inbred C57BL /
Clustered Regularly Interspaced Short Palindromic Repeats /
Multiple Sclerosis: immunology / Multiple Sclerosis:
genetics / Humans / Neuroinflammatory Diseases: genetics /
CRISPR-Cas Systems / Encephalomyelitis, Autoimmune,
Experimental: immunology / Cytokines (NLM Chemicals)},
cin = {AG Simons},
ddc = {610},
cid = {I:(DE-2719)1110008},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41345278},
pmc = {pmc:PMC12880918},
doi = {10.1038/s41593-025-02151-6},
url = {https://pub.dzne.de/record/285047},
}