ORCID: https://orcid.org/0000-0002-1344-0844; Kendirli, Arek ORCID: https://orcid.org/0000-0001-6888-9131; Baygün, Seren; Bauernschmitt, Franz; Thomann, Anna S. ORCID: https://orcid.org/0000-0001-6934-8839; Kisioglu, Ilgin; Beckmann, Daniela; Carpentier Solorio, Yves; Pfaffenstaller, Veronika; Tai, Yi-Heng; Mehraein, Niel; Sanchez, Paula; Spieth, Lena; Gerdes, Lisa Ann ORCID: https://orcid.org/0000-0002-7053-3924; Beltran, Eduardo ORCID: https://orcid.org/0000-0002-7266-4098; Dornmair, Klaus ORCID: https://orcid.org/0000-0003-0342-5373; Simons, Mikael ORCID: https://orcid.org/0000-0001-5329-192X; Peters, Anneli ORCID: https://orcid.org/0000-0002-8259-2219; Schmidt-Supprian, Marc ORCID: https://orcid.org/0000-0002-8543-6166 und Kerschensteiner, Martin ORCID: https://orcid.org/0000-0003-4898-9383
(2026):
In vivo CRISPR screen reveals regulation of macrophage states in neuroinflammation.
In: Nature Neuroscience, Vol. 29: pp. 493-509
[PDF, 21MB]
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.
| Item Type: | Journal article |
|---|---|
| EU Funded Grant Agreement Number: | 682435 |
| Faculties: | Medicine > Biomedical Center Medicine > Medical Center of the University of Munich > Institut für Klinische Neuroimmunologie Medicine > Munich Cluster for Systems Neurology (SyNergy) Medicine > Institute for Stroke and Dementia Research (ISD) |
| Research Centers: | Graduate School of Systemic Neurosciences (GSN) |
| Subjects: | 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-131192-3 |
| ISSN: | 1097-6256 |
| Language: | English |
| Item ID: | 131192 |
| Date Deposited: | 19. Jan 2026 07:27 |
| Last Modified: | 17. Aug 2026 11:46 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 259373024 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 408885537 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 239283807 |
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