Please use this identifier to cite or link to this item:
doi:10.22028/D291-41813
Title: | Identification of the regulatory circuit governing corneal epithelial fate determination and disease |
Author(s): | Smits, Jos G. A. Cunha, Dulce Lima Amini, Maryam Bertolin, Marina Laberthonnière, Camille Qu, Jieqiong Owen, Nicholas Latta, Lorenz Seitz, Berthold Roux, Lauriane N. Stachon, Tanja Ferrari, Stefano Moosajee, Mariya Aberdam, Daniel Szentmary, Nora van Heeringen, Simon J. Zhou, Huiqing |
Language: | English |
Title: | PLOS Biology |
Volume: | 21 |
Issue: | 10 |
Publisher/Platform: | PLOS |
Year of Publication: | 2023 |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
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. |
DOI of the first publication: | 10.1371/journal.pbio.3002336 |
URL of the first publication: | https://doi.org/10.1371/journal.pbio.3002336 |
Link to this record: | urn:nbn:de:bsz:291--ds-418139 hdl:20.500.11880/37405 http://dx.doi.org/10.22028/D291-41813 |
ISSN: | 1545-7885 |
Date of registration: | 27-Mar-2024 |
Faculty: | M - Medizinische Fakultät |
Department: | M - Augenheilkunde |
Professorship: | M - Prof. Dr. Berthold Seitz M - Prof. Dr. med. Nóra Szentmáry |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
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journal.pbio.3002336.pdf | 4,35 MB | Adobe PDF | View/Open |
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