Evidence map›Paper›PMID 40667135›Full record

ArticlebioRxiv : the preprint server for biology2025

L-2-hydroxyglutarate impairs neuronal differentiation through epigenetic activation of

Wen Gu, Xun Wang, Ashley Solmonson, Ling Cai, Yi Xiao, Alpaslan Tasdogan, Jordan Franklin, Yuannyu Zhang, Hua Zhang, Aundrea K Westfall and 13 more

Abstract readPreprint
PubMed Full text at PMC Publisher
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. 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.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Wen GuChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-3003-8945
Xun WangChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ashley SolmonsonChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ling CaiChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yi XiaoChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Alpaslan TasdoganChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jordan FranklinChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yuannyu ZhangChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hua ZhangDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Aundrea K WestfallChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ashley RoweChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hetali TrivediChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Brandon FaubertChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Zheng WuChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jessica SudderthChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lauren G ZachariasChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Bushra AfrozeDepartment of Paediatrics & Child Health, Aga Khan University, Stadium Road, Karachi, Pakistan.
Ilya BezprozvannyDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sunil SudarshanDepartment of Urology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Feng CaiChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Samuel K McBrayerChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Thomas P MathewsChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ralph J DeBerardinisChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Funding

UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V., MINNA, JOHN D. · 1996 to 2024
$57.4M
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WENDY Beth LONDON · 2013 to 2026
$33.5M
University of Texas Southwestern Medical Center SPORE in Kidney CancerP50CA196516 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI James Brugarolas · 2016 to 2026
$24.7M
Metabolic Regulators of Tumor Growth and ProgressionR35CA220449 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI RALPH J DEBERARDINIS · 2017 to 2026
$9.4M
Targeting the neuronal microenvironment in glioblastomaU19CA264504 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy T Batchelor · 2021 to 2026
$6.4M
Regulation of the Kidney Cancer Epigenome by Oncometabolite L-2-HydroxyglutarateR01CA200653 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SUNIL SUDARSHAN · 2016 to 2026
$3.6M
Construction of A Lung Cancer Preclinical Model Cross-comparison PlatformR01CA285336 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Ling Cai · 2024 to 2026
$3.1M
Exploiting Pyrimidine Nucleotide Synthesis Dependence for IDH Mutant Glioma TherapyR01CA258586 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI ABDULLAH, KALIL G, MCBRAYER, SAMUEL KENT · 2021 to 2025
$1.8M
Metabolic mechanisms of glioma progressionR01CA289260 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Kalil G Abdullah, Samuel Kent McBrayer · 2025 to 2026
$1.3M
Defining mechanisms of metabolic-epigenetic crosstalk that drive glioma initiationK99CA277576 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI XIAO, YI · 2023 to 2024
$248k
NCI NIH HHS K99 CA277576NCI NIH HHS P50 CA070907NCI NIH HHS P50 CA165962NCI NIH HHS P50 CA196516NCI NIH HHS R01 CA200653NCI NIH HHS R01 CA258586NCI NIH HHS R01 CA285336NCI NIH HHS R01 CA289260NCI NIH HHS R35 CA220449NCI NIH HHS U19 CA264504
6 · The paper itself

Abstract

High levels of L- and D-2-hydroxyglutarate, the reduced forms of α-ketoglutarate (αKG), are implicated in human neurodevelopmental disorders and cancer. Both enantiomers exert effects on epigenetics by modulating a family of αKG-dependent dioxygenases involved in histone, DNA and RNA demethylation. L-2HG dehydrogenase (L2HGDH) converts L-2HG to αKG. Its deficiency is a rare, autosomal recessive inborn error of metabolism (IEM) characterized by systemic elevations of L-2HG, progressive neurological disability and a high risk of malignancy in the brain. The mechanisms behind these aberrations are unknown. Here we used an isogenic, patient-derived induced pluripotent stem cell (iPSC) system to study the impact of L2HGDH deficiency on neural progenitor cell (NPC) function and neuronal differentiation. We demonstrate that L2HGDH deficiency causes accumulation of L-2HG, NPC hyperproliferation, increased clonogenicity, excessive growth, and defective neuronal differentiation in 2D cultures and cortical spheroids. Editing the

Identifiers

PMID40667135
PMCPMC12262609

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.