Evidence map›Paper›PMID 39814010›Full record

ArticleNeuron2025

CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions.

Emmy Li, Camila Benitez, Steven C Boggess, Mark Koontz, Indigo V L Rose, Delsy Martinez, Nina Dräger, Olivia M Teter, Avi J Samelson, Na'im Pierce and 2 more

Abstract read
In one paragraph

Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
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  10. Review
  11. Article
  12. Defined human tri-lineage brain microtissues.bioRxiv : the preprint server for biology · 2025
    Article
  13. Review
  14. Review
  15. Review
  16. CRISPRi: a way to integrate iPSC-derived neuronal models.Biochemical Society transactions · 2024
    Review
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Emmy LiInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Camila BenitezTETRAD Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Steven C BoggessInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Mark KoontzDepartment of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Indigo V L RoseInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Delsy MartinezDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Nina DrägerInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Olivia M TeterInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, CA, USA.
Avi J SamelsonInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Na'im PierceInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA; FirstGen Internship, Emerson Collective, Palo Alto, CA, USA; University of California, Berkeley, Berkeley, CA, USA.
Erik M UllianDepartment of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Martin KampmannInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: martin.kampmann@ucsf.edu.

Funding

Uncovering the Genetic Mechanisms of the Chromosome 17q21.31 Tau Haplotype on Neurodegeneration Risk in FTD and PSPU54NS123746 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHANG, TIMOTHY S · 2021 to 2025
$9.4M
Investigating the Functional Impact of AD Risk Genes on Neuro-Vascular InteractionsU01AG072464 · NIA · REGENERATIVE RESEARCH FOUNDATION · PI HARARI, OSCAR, KAMPMANN, MARTIN · 2021 to 2025
$8.7M
Predoctoral Training in NeurobiologyT32NS115706 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAMUEL JEREMY PLEASURE · 2020 to 2026
$3.4M
Novel patient-derived 3D platform for detecting TDP-43 proteinopathy and associated biomarkers for ALS/FTDR44NS124457 · NINDS · SYNAPTICURE, INC. · PI GHAFFARI, LAYLA, ULLIAN, ERIK M · 2022 to 2023
$2.2M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
Functional Characterization of Tau Mutation and Post-translational ModificationsR00AG080116 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Avi Jacob Samelson · 2025 to 2026
$487k
Functional Characterization of Tau Mutation and Post-translational ModificationsK99AG080116 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAMELSON, AVI JACOB · 2023 to 2024
$246k
Mechanisms of tau misfolding in neurons elucidated by deep mutational scanning and CRISPR screeningF32AG063487 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAMELSON, AVI JACOB · 2019 to 2021
$195k
NIA NIH HHS F32 AG063487NIA NIH HHS K99 AG080116NIA NIH HHS R00 AG080116NIA NIH HHS U01 AG072464NIH HHS S10 OD028511NINDS NIH HHS R44 NS124457NINDS NIH HHS T32 NS115706NINDS NIH HHS U54 NS123746
6 · The paper itself

Abstract

The complexity of the human brain makes it challenging to understand the molecular mechanisms underlying brain function. Genome-wide association studies have uncovered variants associated with neurological phenotypes. Single-cell transcriptomics have provided descriptions of changes brain cells undergo during disease. However, these approaches do not establish molecular mechanism. To facilitate the scalable interrogation of causal molecular mechanisms in brain cell types, we developed a 3D co-culture system of induced pluripotent stem cell (iPSC)-derived neurons and glia, termed iAssembloids. Using iAssembloids, we ask how glial and neuronal cells interact to control neuronal death and survival. Our CRISPRi-based screens identified that GSK3β inhibits the protective NRF2-mediated oxidative stress response elicited by high neuronal activity. We then investigate the role of APOE-ε4, a risk variant for Alzheimer's disease, on neuronal survival. We find that APOE-ε4-expressing astrocytes may promote neuronal hyperactivity as compared with APOE-ε3-expressing astrocytes. This platform allows for the unbiased identification of mechanisms of neuron-glia cell interactions.

Indexed as

Cell CommunicationCRISPR-Cas SystemsInduced Pluripotent Stem CellsNeurogliaNeuronsAnimalsApolipoprotein E4AstrocytesCells, CulturedCoculture TechniquesGlycogen Synthase Kinase 3 betaHumansNF-E2-Related Factor 2Oxidative StressApolipoprotein E4Glycogen Synthase Kinase 3 betaNF-E2-Related Factor 2APOECRISPR interferenceCROP-seqessential genesfunctional genomicsGSK3Bneuronal activityneuron-glia co-cultureNFE2L2oxidative stress

Identifiers

PMID39814010
PMCPMC11886924

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.