Evidence map›Paper›PMID 41659455›Full record

ArticlebioRxiv : the preprint server for biology2025

Genetic regulators of neuronal survival across metabolic environments.

Neal Bennett, Yanilka Soto-Muniz, Jonathan X Meng, Megan Lee, Joyce Yang, Will R Flanigan, Alexander R Pico, Isha H Jain, Ken Nakamura

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–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, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Neal BennettGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Yanilka Soto-MunizGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Jonathan X MengGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Megan LeeGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Joyce YangGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Will R FlaniganGladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA.
Alexander R PicoInstitute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA, USA.ORCID 0000-0001-5706-2163
Isha H JainGladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA.
Ken NakamuraGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.ORCID 0000-0003-3120-4164

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
UCSF IRACDA Scholars ProgramK12GM081266 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond M. Esquerra, HOLLY A. INGRAHAM · 2007 to 2026
$19.4M
Defining Strategies to Target Energy Failure in Metabolically Vulnerable Human CellsR01AG065428 · NIA · J. DAVID GLADSTONE INSTITUTES · PI NAKAMURA, KEN · 2020 to 2024
$3.7M
Metabolic Vulnerability and Effects of APOE in Human Neurons with Impaired Endocytic RecyclingK01AG078485 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI Neal Bennett · 2022 to 2026
$643k
BD FACSAria II Flow CytometerS10RR028962 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI CAVROIS, MARIELLE · 2011 to 2011
$544k
Bioenergetic and Proteolytic Impact of Ubiquitin-like Pathways in Metabolically Stressed NeuronsF32AG063457 · NIA · J. DAVID GLADSTONE INSTITUTES · PI BENNETT, NEAL · 2019 to 2021
$155k
NCRR NIH HHS S10 RR028962NIAID NIH HHS P30 AI027763NIA NIH HHS F32 AG063457NIA NIH HHS K01 AG078485NIA NIH HHS R01 AG065428NIGMS NIH HHS K12 GM081266
6 · The paper itself

Abstract

Cellular energy metabolism and oxygen availability shape neuronal function and vulnerability, yet the genetic regulators of these metabolic processes in human neurons remain incompletely understood. Here, we performed CRISPR interference (CRISPRi) screens in human induced pluripotent stem cell (iPSC)-derived neurons across four distinct metabolic conditions and at three physiologically relevant oxygen tensions. This combinatorial approach enabled systematic interrogation of gene-environment interactions that govern neuronal metabolic adaptation. We identified genes-including genes associated with Leigh syndrome and autism spectrum disorder-whose importance for cell survival is highly sensitive to environmental context, revealing potential mechanisms underlying metabolic specification and selective neuronal vulnerability in neurological disorders. Our screens also uncovered regulators of neuronal glycolysis, including

Identifiers

PMID41659455
PMCPMC12880232

What OpenQuestion holds

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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.