Evidence map›Paper›PMID 37398204›Full record

ArticlebioRxiv : the preprint server for biology2024

CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis.

Avi J Samelson, Nabeela Ariqat, Justin McKetney, Gita Rohanitazangi, Celeste Parra Bravo, Rudra Bose, Kyle J Travaglini, Victor L Lam, Darrin Goodness, Gary Dixon and 16 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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 36 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 6 institutions in 1 country.

Avi J SamelsonInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Nabeela AriqatInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Justin McKetneyUniversity of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, USA.
Gita RohanitazangiInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Celeste Parra BravoInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Rudra BoseInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Kyle J TravagliniAllen Institute for Brain Science, Seattle, WA, USA.
Victor L LamDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
Darrin GoodnessInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Gary DixonInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Emily MarzetteInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Julianne JinInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Ruilin TianInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Eric TseInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Romany AbskharonDepartments of Chemistry and Biochemistry and Biological Chemistry, UCLA-DOE Institute, UCLA, Los Angeles, CA USA.
Henry PanInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Emma C CarrollInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
Rosalie E LawrenceDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
Jason E GestwickiInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
David EisenbergDepartments of Chemistry and Biochemistry and Biological Chemistry, UCLA-DOE Institute, UCLA, Los Angeles, CA USA.
Nicholas M KanaanDepartment of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
Daniel R SouthworthInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
John D GrossDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
Li GanHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Danielle L SwaneyUniversity of California San Francisco, Quantitative Biosciences Institute (QBI), San Francisco, CA, USA.
Martin KampmannInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.ORCID 0000-0002-3819-7019
University of California, San Francisco · USGladstone Institutes · USHoward Hughes Medical Institute · USAllen Institute for Brain Science · USCornell University · USMichigan State University · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
Topographic, cell type and molecular pathway characterization ofAlzheimer's disease using single cell transcriptomics and epigenomicsU19AG060909 · NIA · ALLEN INSTITUTE · PI Michael Hawrylycz · 2020 to 2026
$83.6M
Project 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Yifan Cheng · 2022 to 2026
$35.7M
Project 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI KOSIK, KENNETH STEPHEN · 2016 to 2020
$10.8M
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
Interdisciplinary Research Network on Biologically Active Tau Aggregate Polymorphs from Alzheimer's Disease and Related DementiasU24AG072458 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI EISENBERG, DAVID, KAYED, RAKEZ · 2021 to 2025
$7.8M
Systematic elucidation of endosomal trafficking as a therapeutic opportunity in AD using CRISPR-based functional genomicsR01AG062359 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMPMANN, MARTIN · 2018 to 2022
$3.2M
Integrative Program in Complex Biological System (ipCBS)T32EB009383 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSHALL, WALLACE, WEINER, ORION D · 2009 to 2022
$3.2M
Molecular mechanisms of selective vulnerability of neurons to tauopathyR01AG082141 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CARLO L CONDELLO, Martin Kampmann · 2023 to 2026
$3.0M
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
Molecular recognition of pathological tau fibril conformationsF32AG076281 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CARROLL, EMMA C · 2022 to 2023
$99k
NCI NIH HHS P30 CA082103NIAID NIH HHS U54 AI170792NIA NIH HHS F32 AG063487NIA NIH HHS F32 AG076281NIA NIH HHS K99 AG080116NIA NIH HHS R01 AG062359NIA NIH HHS R01 AG082141NIA NIH HHS U19 AG060909NIA NIH HHS U24 AG072458NIBIB NIH HHS T32 EB009383NINDS NIH HHS U54 NS100717NINDS NIH HHS U54 NS123746
6 · The paper itself

Abstract

Aggregation of the protein tau defines tauopathies, which include Alzheimer's disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to tau aggregation and subsequent dysfunction and death, but the underlying mechanisms are unknown. To systematically uncover the cellular factors controlling the accumulation of tau aggregates in human neurons, we conducted a genome-wide CRISPRi-based modifier screen in iPSC-derived neurons. The screen uncovered expected pathways, including autophagy, but also unexpected pathways, including UFMylation and GPI anchor synthesis. We discover that the E3 ubiquitin ligase CUL5

Identifiers

PMID37398204
PMCPMC10312804
OpenAlexW4381054560

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.