UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

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. Green open access

[thumbnail of journal.pbio.3002336.pdf]
Preview
PDF
journal.pbio.3002336.pdf - Published Version

Download (4MB) | Preview

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.ucl.ac.uk/id/eprint/10180939
Downloads since deposit
4Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item