Identification of the regulatory circuit governing corneal epithelial fate determination and disease trackhub and additional data
DOI10.5281/zenodo.8353116Zenodo8353116MaRDI QIDQ6681730FDOQ6681730
Dataset published at Zenodo repository.
Simon J van Heeringen, Berthold Seitz, Dulce Lima Cunha, Daniel Aberdam, Jos Smits, Marina Bertolin, Tanja Stachon, Jieqiong Qu, Lorenz Latta, Camille Laberthonnière, Nicholas Owen, Nora Szentmary, Maryam Amini, Stefano Ferrari, Huiqing Jo Zhou, Lauriane N Roux, Mariya Moosajee
Publication date: 31 August 2023
Copyright license: Creative Commons Attribution 4.0 International
The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells, while the non-transparent 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 limbal stem cells 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 that define specific cell fates, and established their regulatory hierarchy. Single-cell RNA-seq analyses of the cornea and the epidermis confirmed these shared and cell type-specific transcription factors. Notably, the shared and limbal stem cell-specific transcription factors 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 limbal stem cell fate and its association with corneal opacity. Files present are within the UCSC trackhub format containing bigwig and bignarrowpeak files associated with the publication: Multi-omics analyses identify transcription factor interplay in corneal epithelial fate determination and disease doi: https://doi.org/10.1101/2022.07.13.499857
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