Evidence map›Paper›PMID 36595669›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Dry eye disease in mice activates adaptive corneal epithelial regeneration distinct from constitutive renewal in homeostasis.

Joseph B Lin, Xiaolei Shen, Charles W Pfeifer, Fion Shiau, Andrea Santeford, Philip A Ruzycki, Brian S Clark, Qin Liu, Andrew J W Huang, Rajendra S Apte

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
15.1field-weighted citation impact, top 1% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
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  10. TAZ (bioRxiv : the preprint server for biology · 2026
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  16. Accumulation of Epigenetic Noise in the Aging Corneal Epithelium and Its Possible Mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
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  18. IFITM1/OVOL1 Axis Is a Novel Regulator of the Expansion of the Limbal Epithelial Stem/Early Transient Amplifying Cell Population.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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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

10 authors at 1 institution in 1 country.

Joseph B LinJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0001-6667-9018
Xiaolei ShenCenter for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110.
Charles W PfeiferJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0002-7579-2984
Fion ShiauJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0003-0848-6562
Andrea SantefordJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0002-7691-6213
Philip A RuzyckiJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0003-3520-6407
Brian S ClarkJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0002-7291-2055
Qin LiuJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0002-1589-0881
Andrew J W HuangJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0003-1939-9149
Rajendra S ApteJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0003-2281-2336
Washington University in St. Louis · US

Funding

WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
NATIONAL RESEARCH SERVICE AWARD-MEDICAL SCIENTISTT32GM007200 · NIGMS · WASHINGTON UNIVERSITY · PI YOKOYAMA, WAYNE M. · 1985 to 2024
$59.8M
WASHINGTON UNIVERSITY CENTER VISION RESEARCHP30EY002687 · NEI · WASHINGTON UNIVERSITY · PI Steven Bassnett · 1985 to 2026
$18.4M
Research Training Program in the Vision SciencesT32EY013360 · NEI · WASHINGTON UNIVERSITY · PI SHIMING CHEN, Daniel Kerschensteiner · 2000 to 2026
$5.6M
The Neural Basis of Ocular SensationsR01EY024704 · NEI · WASHINGTON UNIVERSITY · PI LIU, QIN · 2014 to 2024
$4.3M
THE IMPORTANCE OF MACROPHAGE SENESCENCE IN REGULATING ANGIOGENESIS IN THE EYER01EY019287 · NEI · WASHINGTON UNIVERSITY · PI APTE, RAJENDRA S · 2010 to 2021
$3.9M
Identification of the molecular mechanisms mediating intrinsic control of retinal progenitor competenceR00EY027844 · NEI · WASHINGTON UNIVERSITY · PI CLARK, BRIAN S · 2019 to 2021
$739k
Role of stearoyl-CoA desaturase 2 in macrophage-mediated antimicrobial immunityF30DK130282 · NIDDK · WASHINGTON UNIVERSITY · PI LIN, JOSEPH B · 2021 to 2023
$117k
NCATS NIH HHS UL1 TR002345NEI NIH HHS P30 EY002687NEI NIH HHS R00 EY027844NEI NIH HHS R01 EY019287NEI NIH HHS R01 EY024704NEI NIH HHS T32 EY013360NIDDK NIH HHS F30 DK130282NIGMS NIH HHS T32 GM007200
6 · The paper itself

Abstract

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury. In homeostasis, we capture the transcriptional states that accomplish continuous tissue turnover. We leverage our dataset to identify candidate genes and gene networks that characterize key stages across homeostatic renewal, including markers for LSCs. In aging and diabetes, there were only mild changes with <15 dysregulated genes. The constitutive cell types that accomplish homeostatic renewal were conserved in DED but were associated with activation of cell states that comprise "adaptive regeneration." We provide global markers that distinguish cell types in homeostatic renewal vs. adaptive regeneration and markers that specifically define DED-elicited proliferating and differentiating cell types. We validate that expression of SPARC, a marker of adaptive regeneration, is also induced in corneal epithelial wound healing and accelerates wound closure in a corneal epithelial cell scratch assay. Finally, we propose a classification system for LSC markers based on their expression fidelity in homeostasis and disease. This transcriptional dissection uncovers the dramatically altered transcriptional landscape of the corneal epithelium in DED, providing a framework and atlas for future study of these ocular surface stem cells in health and disease.

Indexed as

Dry Eye SyndromesEpithelium, CornealLimbus CorneaeAnimalsCell DifferentiationCorneaHomeostasisMiceWound Healingcorneadry eyeepitheliumlimbalstem cell

Identifiers

PMID36595669
PMCPMC9926235
OpenAlexW4313527991

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.