Evidence map›Paper›PMID 42526428›Full record

ArticleNeuron2026

Transcriptional regulation of disease-relevant microglial activation programs.

Amanda McQuade, Reet Mishra, Venus Hagan, Weiwei Liang, Peter J Colias, Vincent Cele Castillo, Bianca Gonzalez, Justin P Lubin, Verena Haage, Victoria Marshe and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Amanda McQuadeInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Reet MishraInstitute 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.
Venus HaganInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Weiwei LiangInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Peter J ColiasDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Vincent Cele CastilloInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Bianca GonzalezInstitute 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.
Justin P LubinDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA.
Verena HaageCenter 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.
Victoria MarsheCenter 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.
Masashi FujitaCenter 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.
Thomas TaInstitute 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.
Layla GomesInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Olivia TeterInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Xia HanProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nathaniel RobichaudNomic Bio, Montreal, QC, Canada.
Sarah E ChasinsDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Jessica E RexachProgram 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.
Philip L De JagerCenter 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.
James K NuñezDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Martin KampmannInstitute 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.

Funding

Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI ADAM L. BOXER · 2019 to 2026
$120.9M
Early Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9M
Investigating regional and cellular vulnerabilities to tau pathology in young-onset Alzheimer's diseaseR01AG075802 · NIA · MAYO CLINIC JACKSONVILLE · PI BERNARDINO Francesco GHETTI, Lea Tenenholz Grinberg · 2022 to 2026
$15.5M
Hippocampal iPSC-Derived Assembloids to Model Interneuron and Circuit Vulnerability in Genetically-Encoded Amnestic and Behavioral DementiaRF1NS144499 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REXACH, JESSICA E · 2025 to 2025
$3.1M
Mechanisms of epigenetic memory in human cellsR35GM155044 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI James Karlo Nunez · 2024 to 2026
$1.2M
NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062422NIA NIH HHS R01 AG075802NIA NIH HHS U01 AG057195NIA NIH HHS U19 AG063911NIGMS NIH HHS R35 GM155044NINDS NIH HHS RF1 NS144499
6 · The paper itself

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.

Indexed as

CRISPRdisease-associated microgliaDNMT1interferonmicrogliamicroglial activationphagocytosisPRDM1STAT2ZNF532

Identifiers

PMID42526428
PMCPMC13505846

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.