Evidence map›Paper›PMID 31163126›Full record

ArticleDevelopmental biology2019

Transcriptional profiling of murine retinas undergoing semi-synchronous cone photoreceptor differentiation.

Michael L Kaufman, Ko Uoon Park, Noah B Goodson, Shereen Chew, Stephanie Bersie, Kenneth L Jones, Deepak A Lamba, Joseph A Brzezinski

Open access · greenAbstract read
In one paragraph

Article in Developmental biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.9field-weighted citation impact, top 26% of its field
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

17 citing papers in PubMed, 34 citations in OpenAlex.

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  5. Stimulating the regenerative capacity of the human retina with proneural transcription factors in 3D cultures.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  9. A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 ocular retardation J mice.Developmental dynamics : an official publication of the American Association of Anatomists · 2023
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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

8 authors at 2 institutions in 1 country.

Michael L KaufmanDepartment of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ko Uoon ParkDepartment of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Noah B GoodsonDepartment of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Shereen ChewEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Ophthalmology, University of California, San Francisco, CA, USA.
Stephanie BersieDepartment of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Kenneth L JonesDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Deepak A LambaEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Ophthalmology, University of California, San Francisco, CA, USA.
Joseph A BrzezinskiDepartment of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: Joseph.Brzezinski@ucdenver.edu.
University of Colorado Anschutz Medical Campus · USUniversity of California, San Francisco · US

Funding

Rapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAMBA, DEEPAK ASHOK · 1985 to 2024
$16.8M
Mechanisms of cell fate specification and competence regulation in photoreceptorsR01EY024272 · NEI · UNIVERSITY OF COLORADO DENVER · PI Joseph A Brzezinski · 2014 to 2026
$5.3M
Enhancing photoreceptor integration using microglia-derived secreted factorsR01EY025779 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAMBA, DEEPAK ASHOK · 2016 to 2020
$2.4M
Neuroscience Training GrantT32NS099042 · NINDS · UNIVERSITY OF COLORADO DENVER · PI Nidia Calero, GIDON S FELSEN · 2016 to 2026
$2.1M
NEI NIH HHS P30 EY002162NEI NIH HHS R01 EY024272NEI NIH HHS R01 EY025779NINDS NIH HHS T32 NS099042
6 · The paper itself

Abstract

Uncovering the gene regulatory networks that control cone photoreceptor formation has been hindered because cones only make up a few percent of the retina and form asynchronously during development. To overcome these limitations, we used a γ-secretase inhibitor, DAPT, to disrupt Notch signaling and force proliferating retinal progenitor cells to rapidly adopt neuronal identity. We treated mouse retinal explants at the peak of cone genesis with DAPT and examined tissues at several time-points by histology and bulk RNA-sequencing. We found that this treatment caused supernumerary cone formation in an overwhelmingly synchronized fashion. This analysis revealed several categorical patterns of gene expression changes over time relative to DMSO treated control explants. These were placed in the temporal context of the activation of Otx2, a transcription factor that is expressed at the onset of photoreceptor development and that is required for both rod and cone formation. One group of interest had genes, such as Mybl1, Ascl1, Neurog2, and Olig2, that became upregulated by DAPT treatment before Otx2. Two other groups showed upregulated gene expression shortly after Otx2, either transiently or permanently. This included genes such as Mybl1, Meis2, and Podxl. Our data provide a developmental timeline of the gene expression events that underlie the initial steps of cone genesis and maturation. Applying this strategy to human retinal organoid cultures was also sufficient to induce a massive increase in cone genesis. Taken together, our results provide a temporal framework that can be used to elucidate the gene regulatory logic controlling cone photoreceptor development.

Indexed as

Gene Expression ProfilingAmyloid Precursor Protein SecretasesAnimalsCell DifferentiationEmbryo, MammalianEnzyme InhibitorsFemaleGene Expression Regulation, DevelopmentalHumansMiceOrganoidsOtx Transcription FactorsRetinal Cone Photoreceptor CellsTime FactorsUp-RegulationAmyloid Precursor Protein SecretasesEnzyme InhibitorsOtx2 protein, mouseOtx Transcription FactorsCone photoreceptorFate specificationRetinal developmentRetinal organoidRNA-Seqγ-secretase inhibition

Identifiers

PMID31163126
PMCPMC7722777
OpenAlexW2947648070

What OpenQuestion holds

Textmetadata
LicenceTDM
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.