Evidence map›Paper›PMID 33388438›Full record

ArticleThe ocular surface2021

Single-cell transcriptomics identifies limbal stem cell population and cell types mapping its differentiation trajectory in limbal basal epithelium of human cornea.

De-Quan Li, Sangbae Kim, Jin-Miao Li, Qianmiao Gao, Jongsu Choi, Fang Bian, Jiaoyue Hu, Yun Zhang, Jin Li, Rong Lu and 4 more

Open access · greenAbstract read
In one paragraph

Article in The ocular surface, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
5.7field-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

74 citing papers in PubMed, 111 citations in OpenAlex.

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  18. Recent Advances in Stem Cells of Corneal Epithelia.Investigative ophthalmology & visual science · 2025
    Review
  19. Article
  20. Article

14 more citing papers are in PubMed but not listed here.

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

14 authors at 3 institutions in 2 countries.

De-Quan LiOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA. Electronic address: dequanl@bcm.edu.
Sangbae KimHGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Jin-Miao LiOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Qianmiao GaoDepartment of Biostatistics & Data Science, University of Texas HSC, School of Public Health, Houston, TX, USA.
Jongsu ChoiHGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Fang BianOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Jiaoyue HuOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Yun ZhangOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Jin LiOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Rong LuOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Yumei LiHGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Stephen C PflugfelderOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Hongyu MiaoDepartment of Biostatistics & Data Science, University of Texas HSC, School of Public Health, Houston, TX, USA.
Rui ChenHGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address: ruichen@bcm.edu.
Baylor College of Medicine · USSun Yat-sen University · CNThe University of Texas Health Science Center at Houston · US

Funding

VISION RESEARCH CENTERP30EY002520 · NEI · BAYLOR COLLEGE OF MEDICINE · PI Samuel M Wu · 1985 to 2026
$14.8M
PATHOGENESIS OF CONJUNCTIVAL SQUAMOUS METAPLASIAR01EY011915 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI PFLUGFELDER, STEPHEN C · 1997 to 2023
$8.0M
GENETICS OF EARLY ONSET RETINAL DISEASESR01EY018571 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI RUI CHEN · 2008 to 2026
$7.2M
Molecular Basis of Human Visual System DisordersR01EY022356 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI RUI CHEN · 2012 to 2026
$6.1M
TLR4-DEPENDENT INNATE IMMUNITY IN POLLEN-TRIGGERED OCULAR ALLERGIC INFLAMMATIONR01EY023598 · NEI · BAYLOR COLLEGE OF MEDICINE · PI LI, DE-QUAN · 2014 to 2018
$2.1M
High Throughput Genomic Sequencer at BCM Core FacilityS10OD023469 · OD · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI · 2017 to 2017
$600k
Acquisition of the Fluidigm system to accelerate functional genomics researchS10OD018033 · OD · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI · 2014 to 2014
$396k
NEI NIH HHS P30 EY002520NEI NIH HHS R01 EY011915NEI NIH HHS R01 EY018571NEI NIH HHS R01 EY022356NEI NIH HHS R01 EY023598NIH HHS S10 OD018033NIH HHS S10 OD023469
6 · The paper itself

Abstract

purposeThis study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution.

methodsSingle cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis. Tissue RNA in situ hybridization with RNAscope, immunofluorescent staining and multiple functional assays were performed using human corneas and limbal epithelial culture models.

resultsSingle-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters belonging to three lineages. A smallest cluster (0.4% of total cells) was identified as LSCs based on their quiescent and undifferentiated states with enriched marker genes for putative epithelial stem cells. TSPAN7 and SOX17 are discovered and validated as new LSC markers based on their exclusive expression pattern and spatial localization in limbal basal epithelium by RNAscope and immunostaining, and functional role in cell growth and tissue regeneration models with RNA interference in cultures. Interestingly, five cell types/states mapping a developmental trajectory of LSC from quiescence to proliferation and differentiation are uncovered by Monocle3 and CytoTRACE pseudotime analysis. The transcription factor networks linking novel signaling pathways are revealed to maintain LSC stemness.

conclusionsThis human corneal scRNA-Seq identifies the LSC population and uncovers novel cell types mapping the differentiation trajectory in heterogenous limbal basal epithelium. The findings provide insight into LSC concept and lay the foundation for understanding the corneal homeostasis and diseases.

Indexed as

Epithelium, CornealLimbus CorneaeCell DifferentiationCorneaHumansStem CellsTranscriptomeAdult stem cellsCorneaEpitheliumLimbal stem cellsSingle-cell transcriptomics

Identifiers

PMID33388438
PMCPMC8359589
OpenAlexW3117173614

What OpenQuestion holds

Textmetadata
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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.