Evidence map›Paper›PMID 37856539›Full record

ArticlePLoS biology2023

Identification of the regulatory circuit governing corneal epithelial fate determination and disease.

Jos G A Smits, Dulce Lima Cunha, Maryam Amini, Marina Bertolin, Camille Laberthonnière, Jieqiong Qu, Nicholas Owen, Lorenz Latta, Berthold Seitz, Lauriane N Roux and 7 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

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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

17 authors at 7 institutions in 5 countries.

Jos G A SmitsFaculty of Science, Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Dulce Lima CunhaFaculty of Science, Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Maryam AminiDr. Rolf M. Schwiete Center for Limbal Stem Cell and Aniridia Research, Saarland University, Homburg/Saar, Germany.
Marina BertolinFondazione Banca degli Occhi del Veneto, Venice, Italy.
Camille LaberthonnièreFaculty of Science, Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Jieqiong QuFaculty of Science, Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Nicholas OwenDevelopment, Ageing and Disease, UCL Institute of Ophthalmology, London, United Kingdom.
Lorenz LattaDr. Rolf M. Schwiete Center for Limbal Stem Cell and Aniridia Research, Saarland University, Homburg/Saar, Germany.
Berthold SeitzDepartment of Ophthalmology, Saarland University Medical Center, UKS, Homburg, Germany.
Lauriane N RouxINSERM U976, Paris, France.
Tanja StachonDr. Rolf M. Schwiete Center for Limbal Stem Cell and Aniridia Research, Saarland University, Homburg/Saar, Germany.
Stefano FerrariFondazione Banca degli Occhi del Veneto, Venice, Italy.
Mariya MoosajeeDevelopment, Ageing and Disease, UCL Institute of Ophthalmology, London, United Kingdom.
Daniel AberdamINSERM U976, Paris, France.
Nora SzentmaryDr. Rolf M. Schwiete Center for Limbal Stem Cell and Aniridia Research, Saarland University, Homburg/Saar, Germany.
Simon J van HeeringenFaculty of Science, Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Huiqing ZhouFaculty of Science, Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, the Netherlands.
Saarland University · DEInserm · FRRadboud Institute for Molecular Life Sciences · NLRadboud University Medical Center · NLRadboud University Nijmegen · NLUniversity College London · GBVeneto Eye Bank Foundation · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells (LSCs), while the nontransparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human LSCs from the cornea and keratinocytes from the epidermis and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors (TFs) that define specific cell fates and established their regulatory hierarchy. Single-cell RNA-seq (scRNA-seq) analyses of the cornea and the epidermis confirmed these shared and cell type-specific TFs. Notably, the shared and LSC-specific TFs can cooperatively target genes associated with corneal opacity. Importantly, we discovered that FOSL2, a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the LSC fate and its association with corneal opacity.

Indexed as

Corneal OpacityEpithelium, CornealLimbus CorneaeCell DifferentiationCorneaHumansTranscription FactorsTranscription Factors

Identifiers

PMID37856539
PMCPMC10586658
OpenAlexW4387770961

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.