Smits, JGA;
Cunha, DL;
Amini, M;
Bertolin, M;
Laberthonnière, C;
Qu, J;
Owen, N;
... Zhou, H; + view all
(2023)
Identification of the regulatory circuit governing corneal epithelial fate determination and disease.
PLoS Biology
, 21
(10)
, Article e3002336. 10.1371/journal.pbio.3002336.
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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.
| Type: | Article |
|---|---|
| Title: | Identification of the regulatory circuit governing corneal epithelial fate determination and disease |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pbio.3002336 |
| Publisher version: | https://doi.org/10.1371/journal.pbio.3002336 |
| Language: | English |
| Additional information: | © 2023 Smits et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Humans, Limbus Corneae, Cornea, Epithelium, Corneal, Transcription Factors, Cell Differentiation, Corneal Opacity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10180939 |
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