Home > Publications Database > In vivo CRISPR screen reveals regulation of macrophage states in neuroinflammation. > print

001     285047
005     20260304110134.0
024 7 _ |a 10.1038/s41593-025-02151-6
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024 7 _ |a 1546-1726
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037 _ _ |a DZNE-2026-00171
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a de la Rosa, Clara
|0 0000-0002-1344-0844
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245 _ _ |a In vivo CRISPR screen reveals regulation of macrophage states in neuroinflammation.
260 _ _ |a New York, NY
|c 2026
|b Nature America
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520 _ _ |a 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.
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650 _ 7 |a Cytokines
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Macrophages: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Cytokines: metabolism
|2 MeSH
650 _ 2 |a Cytokines: genetics
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Clustered Regularly Interspaced Short Palindromic Repeats
|2 MeSH
650 _ 2 |a Multiple Sclerosis: immunology
|2 MeSH
650 _ 2 |a Multiple Sclerosis: genetics
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Neuroinflammatory Diseases: genetics
|2 MeSH
650 _ 2 |a CRISPR-Cas Systems
|2 MeSH
650 _ 2 |a Encephalomyelitis, Autoimmune, Experimental: immunology
|2 MeSH
700 1 _ |a Kendirli, Arek
|0 0000-0001-6888-9131
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700 1 _ |a Baygün, Seren
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700 1 _ |a Bauernschmitt, Franz
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700 1 _ |a Thomann, Anna S
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700 1 _ |a Kisioglu, Ilgin
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700 1 _ |a Beckmann, Daniela
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700 1 _ |a Carpentier Solorio, Yves
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700 1 _ |a Pfaffenstaller, Veronika
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700 1 _ |a Tai, Yi-Heng
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700 1 _ |a Mehraein, Niel
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700 1 _ |a Sanchez, Paula
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700 1 _ |a Spieth, Lena
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700 1 _ |a Gerdes, Lisa Ann
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700 1 _ |a Beltran, Eduardo
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700 1 _ |a Dornmair, Klaus
|0 0000-0003-0342-5373
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700 1 _ |a Simons, Mikael
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700 1 _ |a Peters, Anneli
|0 0000-0002-8259-2219
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700 1 _ |a Schmidt-Supprian, Marc
|0 0000-0002-8543-6166
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700 1 _ |a Kerschensteiner, Martin
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773 _ _ |a 10.1038/s41593-025-02151-6
|g Vol. 29, no. 2, p. 493 - 509
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|t Nature neuroscience
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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