Evidence map›Paper›PMID 34653711›Full record

ArticleThe ocular surface2022

High expression of SARS-CoV2 viral entry-related proteins in human limbal stem cells.

Yuzuru Sasamoto, Catherine A A Lee, Masahito Yoshihara, Gabrielle Martin, Bruce R Ksander, Markus H Frank, Natasha Y Frank

Abstract read
In one paragraph

Article in The ocular surface, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Recent Advances in Stem Cells of Corneal Epithelia.Investigative ophthalmology & visual science · 2025
    Review
  2. Review
  3. Article
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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

7 authors.

Yuzuru SasamotoDivision of Genetics, Brigham and Women's Hospital, Boston, MA, United States; Transplant Research Program, Boston Children's Hospital, Boston, MA, United States.
Catherine A A LeeDivision of Genetics, Brigham and Women's Hospital, Boston, MA, United States; Transplant Research Program, Boston Children's Hospital, Boston, MA, United States.
Masahito YoshiharaDepartment of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Gabrielle MartinDivision of Genetics, Brigham and Women's Hospital, Boston, MA, United States; Transplant Research Program, Boston Children's Hospital, Boston, MA, United States.
Bruce R KsanderMassachusetts Eye & Ear Infirmary, Schepens Eye Research Institute, Boston, MA, United States.
Markus H FrankTransplant Research Program, Boston Children's Hospital, Boston, MA, United States; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA; School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.
Natasha Y FrankDivision of Genetics, Brigham and Women's Hospital, Boston, MA, United States; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Department of Medicine, VA Boston Healthcare System, Boston, MA, United States. Electronic address: nyfrank@bwh.harvard.edu.

Funding

VISION RESEARCHP30EY003790 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore · 1985 to 2026
$25.5M
ABCB5-positive stem cells for LSCD therapyR01EY025794 · NEI · BOSTON CHILDREN'S HOSPITAL · PI NATASHA Y FRANK, Markus H. Frank · 2016 to 2026
$6.1M
Multipotent ABCB5-positive cell therapeutics for corneal diseaseR24EY028767 · NEI · BRIGHAM AND WOMEN'S HOSPITAL · PI FRANK, MARKUS H., FRANK, NATASHA Y · 2018 to 2022
$5.9M
Organ Design and Engineering Training Program (ODET Program)T32EB016652 · NIBIB · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 2014 to 2023
$3.5M
Skin-Intrinsic Immunosuppressive Mesenchymal Stem Cells and aGVHDR01HL161087 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI FRANK, MARKUS H., FRANK, NATASHA Y · 2022 to 2025
$1.7M
Development of cell-free approaches to the treatment of limbal stem cell deficiencyK99EY031741 · NEI · BRIGHAM AND WOMEN'S HOSPITAL · PI SASAMOTO, YUZURU · 2020 to 2021
$220k
NEI NIH HHS K99 EY031741NEI NIH HHS P30 EY003790NEI NIH HHS R01 EY025794NEI NIH HHS R24 EY028767NHLBI NIH HHS R01 HL161087NIBIB NIH HHS T32 EB016652RRD VA I01 RX000989
6 · The paper itself

Abstract

purposeCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). While the ocular surface is considered one of the major SARS-CoV2 transmission routes, the specific cellular tropism of SARS-CoV2 is not fully understood. In the current study, we evaluated the expression and regulation of two SARS-CoV2 viral entry proteins, TMPRSS2 and ACE2, in human ocular epithelial cells and stem cells.

methodsTMPRSS2 and ACE2 expression in ABCB5-positive limbal stem cells (LSCs) were assessed by RNAseq, flow cytometry and immunohistochemistry. PAX6, TMPRSS2, and ACE2 mRNA expression values were obtained from the GSE135455 and DRA002960 RNA-seq datasets. siRNA-mediated PAX6 knockdown (KD) was performed in limbal and conjunctival epithelial cells. TMPRSS2 and ACE2 expression in the PAX6 KD cells was analyzed by qRT-PCR and Western blot.

resultsWe found that ABCB5-positive LSCs express high levels of TMPRSS2 and ACE2 compared to ABCB5-negative limbal epithelial cells. Mechanistically, gene knockout and overexpression models revealed that the eye transcription factor PAX6 negatively regulates TMPRSS2 expression. Therefore, low levels of PAX6 in ABCB5-positive LSCs promote TMPRSS2 expression, and high levels of TMPRSS2 and ACE2 expression by LSCs indicate enhanced susceptibility to SARS-CoV2 infection in this stem cell population.

conclusionsOur study points to a need for COVID-19 testing of LSCs derived from donor corneas before transplantation to patients with limbal stem cell deficiency. Furthermore, our findings suggest that expandable human ABCB5+ LSC cultures might represent a relevant novel model system for studying cellular SARS-CoV2 viral entry mechanisms and evaluating related targeting strategies.

Indexed as

COVID-19RNA, ViralATP Binding Cassette Transporter, Subfamily BCOVID-19 TestingHumansSARS-CoV-2Stem CellsViral ProteinsVirus InternalizationABCB5 protein, humanATP Binding Cassette Transporter, Subfamily BRNA, ViralViral ProteinsACE2COVID-19Limbal stem cellsPAX6SARS-CoV2TMPRSS2

Identifiers

PMID34653711
PMCPMC8511872

What Socratic holds

Textmetadata
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.