Evidence map›Paper›PMID 37163077›Full record

ArticlebioRxiv : the preprint server for biology2024

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 Draeger, Olivia M Teter, Avi J Samelson, Na'im Pierce and 2 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 6 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Emmy LiInstitute for Neurodegenerative Diseases, 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.
Delsy MartinezDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Nina DraegerInstitute 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.
Avi J SamelsonInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Na'im PierceFirstGen Internship, Emerson Collective, 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.ORCID 0000-0002-3819-7019
University of California, San Francisco · USUniversity of California, Berkeley · US

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 GESCHWIND, DANIEL H, GOATE, ALISON M · 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
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 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 U01 AG072464NIH HHS S10 OD028511NINDS NIH HHS T32 NS115706NINDS NIH HHS U54 NS123746
6 · The paper itself

Abstract

The sheer complexity of the brain has complicated our ability to understand the cellular and molecular mechanisms underlying its function in health and disease. Genome-wide association studies have uncovered genetic variants associated with specific neurological phenotypes and diseases. In addition, single-cell transcriptomics have provided molecular descriptions of specific brain cell types and the changes they undergo during disease. Although these approaches provide a giant leap forward towards understanding how genetic variation can lead to functional changes in the brain, they do not establish molecular mechanisms. To address this need, we developed a 3D co-culture system termed iAssembloids (induced multi-lineage assembloids) that enables the rapid generation of homogenous neuron-glia spheroids. We characterize these iAssembloids with immunohistochemistry and single-cell transcriptomics and combine them with large-scale CRISPRi-based screens. In our first application, 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 in the presence of reactive oxygen species elicited by high neuronal activity, which was not previously found in 2D monoculture neuron screens. We also apply the platform to investigate the role of APOE-

Indexed as

APOECRISPR interferenceCROP-seqessential genesfunctional genomicsGSK3Bneuronal activityneuron-glia co-cultureNFE2L2oxidative stresssingle-nucleus RNA sequencing

Identifiers

PMID37163077
PMCPMC10168378
OpenAlexW4367182353

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.