The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation
oleh: Mingsen Li, Huizhen Guo, Bofeng Wang, Zhuo Han, Siqi Wu, Jiafeng Liu, Huaxing Huang, Jin Zhu, Fengjiao An, Zesong Lin, Kunlun Mo, Jieying Tan, Chunqiao Liu, Li Wang, Xin Deng, Guigang Li, Jianping Ji, Hong Ouyang
| Format: | Article |
|---|---|
| Diterbitkan: | Nature Portfolio 2024-01-01 |
Deskripsi
Abstract Proper differentiation of corneal epithelial cells (CECs) from limbal stem/progenitor cells (LSCs) is required for maintenance of ocular homeostasis and clear vision. Here, using a single-cell transcriptomic atlas, we delineate the comprehensive and refined molecular regulatory dynamics during human CEC development and differentiation. We find that RORA is a CEC-specific molecular switch that initiates and drives LSCs to differentiate into mature CECs by activating PITX1. RORA dictates CEC differentiation by establishing CEC-specific enhancers and chromatin interactions between CEC gene promoters and distal regulatory elements. Conversely, RORA silences LSC-specific promoters and disrupts promoter-anchored chromatin loops to turn off LSC genes. Collectively, our work provides detailed and comprehensive insights into the transcriptional dynamics and RORA-mediated epigenetic remodeling underlying human corneal epithelial differentiation.