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000285047 1001_ $$00000-0002-1344-0844$$ade la Rosa, Clara$$b0
000285047 245__ $$aIn vivo CRISPR screen reveals regulation of macrophage states in neuroinflammation.
000285047 260__ $$aNew York, NY$$bNature America$$c2026
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000285047 520__ $$aHere 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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000285047 650_7 $$2NLM Chemicals$$aCytokines
000285047 650_2 $$2MeSH$$aAnimals
000285047 650_2 $$2MeSH$$aMacrophages: metabolism
000285047 650_2 $$2MeSH$$aMice
000285047 650_2 $$2MeSH$$aCytokines: metabolism
000285047 650_2 $$2MeSH$$aCytokines: genetics
000285047 650_2 $$2MeSH$$aMice, Inbred C57BL
000285047 650_2 $$2MeSH$$aClustered Regularly Interspaced Short Palindromic Repeats
000285047 650_2 $$2MeSH$$aMultiple Sclerosis: immunology
000285047 650_2 $$2MeSH$$aMultiple Sclerosis: genetics
000285047 650_2 $$2MeSH$$aHumans
000285047 650_2 $$2MeSH$$aNeuroinflammatory Diseases: genetics
000285047 650_2 $$2MeSH$$aCRISPR-Cas Systems
000285047 650_2 $$2MeSH$$aEncephalomyelitis, Autoimmune, Experimental: immunology
000285047 7001_ $$00000-0001-6888-9131$$aKendirli, Arek$$b1
000285047 7001_ $$aBaygün, Seren$$b2
000285047 7001_ $$aBauernschmitt, Franz$$b3
000285047 7001_ $$00000-0001-6934-8839$$aThomann, Anna S$$b4
000285047 7001_ $$aKisioglu, Ilgin$$b5
000285047 7001_ $$aBeckmann, Daniela$$b6
000285047 7001_ $$aCarpentier Solorio, Yves$$b7
000285047 7001_ $$aPfaffenstaller, Veronika$$b8
000285047 7001_ $$aTai, Yi-Heng$$b9
000285047 7001_ $$aMehraein, Niel$$b10
000285047 7001_ $$aSanchez, Paula$$b11
000285047 7001_ $$0P:(DE-2719)9002306$$aSpieth, Lena$$b12$$udzne
000285047 7001_ $$aGerdes, Lisa Ann$$b13
000285047 7001_ $$00000-0002-7266-4098$$aBeltran, Eduardo$$b14
000285047 7001_ $$00000-0003-0342-5373$$aDornmair, Klaus$$b15
000285047 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b16
000285047 7001_ $$00000-0002-8259-2219$$aPeters, Anneli$$b17
000285047 7001_ $$00000-0002-8543-6166$$aSchmidt-Supprian, Marc$$b18
000285047 7001_ $$00000-0003-4898-9383$$aKerschensteiner, Martin$$b19
000285047 773__ $$0PERI:(DE-600)1494955-6$$a10.1038/s41593-025-02151-6$$gVol. 29, no. 2, p. 493 - 509$$n2$$p493 - 509$$tNature neuroscience$$v29$$x1097-6256$$y2026
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