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| Status |
Public on Dec 07, 2020 |
| Title |
Core transcription regulatory circuitry orchestrates stratified epithelial homeostasis (RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Adult stem cell identity, plasticity, and homeostasis are precisely orchestrated by lineage-restricted epigenetic and transcriptional regulatory networks. Here, by integrating super-enhancer and chromatin accessibility landscapes, we delineate core transcription regulatory circuitries (CRCs) of limbal stem/progenitor cells (LSCs) and find that RUNX1 and SMAD3 are required for maintenance of the corneal epithelial identity and homeostasis. RUNX1 or SMAD3 depletion inhibits PAX6 and induces LSCs to differentiate into epidermal-like type. RUNX1, PAX6 and SMAD3 (RPS) interact with each other and synergistically establish a CRC to govern the lineage-specific cis-regulatory atlas. Moreover, RUNX1 shapes LSC chromatin architecture via modulating H3K27ac deposition. Disturbance of RPS cooperation results in cell identity switching and dysfunction of the corneal epithelium, which is strongly linked to various human corneal diseases. Our work highlights CRC TF cooperativity for the establishment of stem cell identity and lineage commitment, and provides comprehensive regulatory principles for human stratified epithelial homeostasis and pathogenesis.
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| Overall design |
RNA-seq for wildtype LSCs and skin epithelial stem cells (SESCs). RNA-seq for scrambled shRNA- and shRUNX1-treated LSCs. RNA-seq for scrambled shRNA- and shSMAD3-treated LSCs.
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| |
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| Citation(s) |
33462242, 35277509, 36652264 |
| |
| Submission date |
Aug 14, 2020 |
| Last update date |
Feb 06, 2023 |
| Contact name |
Mingsen Li |
| E-mail(s) |
lims3@mail2.sysu.edu.cn
|
| Organization name |
Sun Yat-sen University
|
| Department |
Zhongshan Ophthalmic Center
|
| Street address |
No. 7 Jinsui road Tianhe district
|
| City |
Guanzhou |
| ZIP/Postal code |
510060 |
| Country |
China |
| |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE156273 |
Core transcription regulatory circuitry orchestrates stratified epithelial homeostasis |
|
| Relations |
| BioProject |
PRJNA657250 |
| SRA |
SRP277533 |
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