Evidence map›Paper›PMID 40758714›Full record

ArticlePLoS biology2025

Active DNA demethylation upstream of rod-photoreceptor fate determination is required for retinal development.

Ismael Hernández-Núñez, Alaina Urman, Xiaodong Zhang, William Jacobs, Christy Hoffmann, Ellen G Harding, Shiming Chen, Meelad M Dawlaty, Philip A Ruzycki, John R Edwards and 1 more

Abstract read
In one paragraph

Article in PLoS biology, 2025. 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.

  1. Ten-Eleven Translocation Enzymes Control the Rate and Mode of Retinal Progenitor Cell Division in the Developing Retina.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Ismael Hernández-NúñezJohn F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Alaina UrmanDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Xiaodong ZhangJohn F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
William JacobsDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Christy HoffmannJohn F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Ellen G HardingJohn F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Shiming ChenJohn F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Meelad M DawlatyRuth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Philip A RuzyckiJohn F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
John R EdwardsDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Brian S ClarkJohn F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-7291-2055

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
WASHINGTON UNIVERSITY CENTER VISION RESEARCHP30EY002687 · NEI · WASHINGTON UNIVERSITY · PI Steven Bassnett · 1985 to 2026
$18.4M
Vulnerable and Resilient Cells in Retinal DegenerationR01EY012543 · NEI · WASHINGTON UNIVERSITY · PI SHIMING CHEN, Philip Raymond Williams · 2000 to 2026
$12.2M
SUPPORT FOR THE ROSE F KENNEDY IDDRC P50P50HD105352 · NICHD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI SOPHIE MOLHOLM, Steven Upshaw Walkley · 2021 to 2026
$7.0M
Research Training Program in the Vision SciencesT32EY013360 · NEI · WASHINGTON UNIVERSITY · PI SHIMING CHEN, Daniel Kerschensteiner · 2000 to 2026
$5.6M
Understanding and treating CRX-linked retinopathiesR01EY032136 · NEI · WASHINGTON UNIVERSITY · PI CHEN, SHIMING · 2021 to 2025
$1.9M
Regulation of Retinal Development by RNA moleculesR01EY035381 · NEI · WASHINGTON UNIVERSITY · PI Brian S Clark · 2024 to 2026
$1.4M
Homeostasis of the Retinal EpigenomeR01EY036368 · NEI · WASHINGTON UNIVERSITY · PI Philip Andrew Ruzycki · 2024 to 2026
$1.2M
Identification of the molecular mechanisms mediating intrinsic control of retinal progenitor competenceR00EY027844 · NEI · WASHINGTON UNIVERSITY · PI CLARK, BRIAN S · 2019 to 2021
$739k
Single-cell approaches to probe the function of the unique neuronal epigenomeR21NS127191 · NINDS · WASHINGTON UNIVERSITY · PI EDWARDS, JOHN R., GABEL, HARRISON W · 2022 to 2023
$433k
New approaches to determine the function of neuronal epigenetic marksR21NS137254 · NINDS · WASHINGTON UNIVERSITY · PI EDWARDS, JOHN R., GABEL, HARRISON W · 2024 to 2025
$428k
NCATS NIH HHS UL1 TR002345NCI NIH HHS P30 CA091842NEI NIH HHS P30 EY002687NEI NIH HHS R00 EY027844NEI NIH HHS R01 EY012543NEI NIH HHS R01 EY032136NEI NIH HHS R01 EY035381NEI NIH HHS R01 EY036368NEI NIH HHS T32 EY013360NICHD NIH HHS P50 HD105352NINDS NIH HHS R21 NS127191NINDS NIH HHS R21 NS137254
6 · The paper itself

Abstract

Retinal cell fate specification from multipotent retinal progenitors is governed by dynamic changes in chromatin structure and gene expression. Methylation at cytosines in DNA (5mC) is actively regulated for proper control of gene expression and chromatin architecture. Numerous genes display active DNA demethylation across retinal development; a process that requires oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and is controlled by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. Using an allelic series of conditional TET enzyme mutants in mice, we determine that DNA demethylation is required upstream of NRL and NR2E3 expression for the establishment of rod-photoreceptor fate. Using histological, behavioral, transcriptomic, and base-pair resolution DNA methylation analyses, we establish that inhibition of active DNA demethylation results in global changes in gene expression and methylation patterns that prevent photoreceptor precursors from adopting a rod-photoreceptor fate, instead producing a retina in which all photoreceptors specify as cones. Our results establish the TET enzymes and DNA demethylation as critical regulators of retinal development and cell fate specification, elucidating a novel mechanism required for the specification of rod-photoreceptors.

Indexed as

DNA DemethylationRetinaRetinal Rod Photoreceptor Cells5-MethylcytosineAnimalsBasic-Leucine Zipper Transcription FactorsCell DifferentiationDioxygenasesDNA-Binding ProteinsDNA MethylationEye ProteinsGene Expression Regulation, DevelopmentalMiceMice, Inbred C57BLOrphan Nuclear ReceptorsProto-Oncogene Proteins5-hydroxymethylcytosine5-MethylcytosineBasic-Leucine Zipper Transcription FactorsDioxygenasesDNA-Binding ProteinsEye ProteinsNr2e3 protein, mouseNrl protein, mouseOrphan Nuclear ReceptorsProto-Oncogene ProteinsTet2 protein, mouse

Identifiers

PMID40758714
PMCPMC12407554

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.