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| Status |
Public on Sep 22, 2023 |
| Title |
Multi-omics analyses identify transcription factor interplay in corneal epithelial fate determination and disease [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Comparative TF binding analysis of ChIP-seq data for Limbal Stem Cells and Keratinocytes
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| Contributor(s) |
Smits JG, Cunha DL, Amini M, Bertolin M, Laberthonnière C, Qu J, Owen N, Latta L, Seitz B, Roux LN, Stachon T, Ferrari S, Moosajee M, Aberdam D, Szentmary N, van Heeringen SJ, Zhou H |
| Citation(s) |
37856539 |
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| Submission date |
Jun 24, 2022 |
| Last update date |
Oct 26, 2023 |
| Contact name |
Jo Huiqing Zhou |
| E-mail(s) |
jo.zhou@radboudumc.nl
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| Organization name |
Radboud University
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| Street address |
Geert Grooteplein 26/28
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| City |
Nijmegen |
| ZIP/Postal code |
6525GA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE206924 |
Multi-omics analyses identify transcription factor interplay in corneal epithelial fate determination and disease |
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| Relations |
| BioProject |
PRJNA852605 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE206920_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of BW, XLS) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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