{
  "abstract": "Microglia, the brain's innate immune cells, can adopt a wide variety of activation states relevant to health and disease. Dysregulation of microglial activation occurs in numerous brain disorders, and driving or inhibiting specific states could be therapeutic. To discover regulators of microglial activation states, we conducted CRISPR interference screens in induced pluripotent stem cell (iPSC)-derived microglia for inhibitors and activators of six microglial states. We characterized 31 regulators at the single-cell transcriptomic and cell-surface proteome level in two distinct iPSC-derived microglia models, uncovering protein markers of relevant states. We functionally characterized several multi-state regulators. ZNF532 and PRDM1 knockdown drive disease-associated, lipid-rich signatures and enhance phagocytosis while showing opposing effects on antigen-presentation signatures. DNMT1 knockdown results in widespread loss of DNA methylation, activating negative regulators of interferon signaling. These findings provide a framework to direct microglial activation to selectively enrich microglial activation states, define their functional outputs, and inform future therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA",
    "University of California, San Francisco",
    "Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, CA 94158, USA",
    "Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA",
    "University of California, Berkeley",
    "Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Engineering and Technology Department, City College of San Francisco, San Francisco, CA 94112, USA",
    "Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA",
    "Columbia University Irving Medical Center",
    "Center for Translational & Computational Neuroimmunology, Department of Neurology & Taub Institute for the study of Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY 10027, USA",
    "Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA",
    "Nomic Bio, Montreal, QC, Canada",
    "Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA",
    "Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA",
    "Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA",
    "Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Department for Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: martin.kampmann@ucsf.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Amanda McQuade",
      "orcid": "0000-0001-5368-6788"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Reet Mishra",
      "orcid": "0000-0002-8479-1422"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Venus Hagan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Weiwei Liang",
      "orcid": "0009-0000-1187-8095"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Peter J. Colias"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Vincent Cele Castillo"
    },
    {
      "affs": [
        5,
        4
      ],
      "name": "Bianca Gonzalez"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Justin P. Lubin",
      "orcid": "0000-0003-2311-1873"
    },
    {
      "affs": [
        8,
        7
      ],
      "name": "Verena Claudia Haage",
      "orcid": "0000-0001-7569-8421"
    },
    {
      "affs": [
        8,
        7
      ],
      "name": "Victoria S. Marshe",
      "orcid": "0000-0002-1762-4819"
    },
    {
      "affs": [
        8,
        1
      ],
      "name": "Masashi Fujita"
    },
    {
      "affs": [
        5,
        1
      ],
      "name": "Thomas Ta"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Layla Gomes"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Olivia M. Teter",
      "orcid": "0000-0001-8490-2543"
    },
    {
      "affs": [
        9,
        7
      ],
      "name": "Xia Han"
    },
    {
      "affs": [
        10,
        4
      ],
      "name": "Nathaniel Robichaud"
    },
    {
      "affs": [
        11,
        1
      ],
      "name": "Sarah Chasins",
      "orcid": "0000-0003-0557-3580"
    },
    {
      "affs": [
        12
      ],
      "name": "Jessica E. Rexach",
      "orcid": "0000-0002-4462-7249"
    },
    {
      "affs": [
        8
      ],
      "name": "Philip L. De Jager",
      "orcid": "0000-0002-8057-2505"
    },
    {
      "affs": [
        13
      ],
      "name": "James K. Nuñez",
      "orcid": "0000-0002-7396-6119"
    },
    {
      "affs": [
        14
      ],
      "name": "Martin Kampmann",
      "orcid": "0000-0002-3819-7019"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1a0v3j1ctrxvd.bib",
  "cited_by": 6,
  "doi": "10.1016/j.neuron.2026.07.001",
  "fulltext_url": null,
  "id": "1a0v3j1ctrxvd",
  "issns": [
    "0896-6273",
    "1097-4199"
  ],
  "landing_url": "https://doi.org/10.1016/j.neuron.2026.07.001",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
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  "pdf_url": "https://www.cell.com/neuron/pdf/S0896-6273(26)00530-1.pdf",
  "pmcid": "PMC12632903",
  "pmid": "41278975",
  "published": "2026-07-01",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/1a0v3j1ctrxvd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:53Z",
      "native_id": "W4415117433",
      "source": "openalex",
      "url": "https://doi.org/10.1016/j.neuron.2026.07.001"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Transcriptional regulation of disease-relevant microglial activation programs",
  "title_text": "Transcriptional regulation of disease-relevant microglial activation programs",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T13:21:01Z",
  "url": "https://research.draconitic.com/paper/1a0v3j1ctrxvd",
  "venue": "Neuron",
  "versions": []
}