The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation.
Mingsen LiHuizhen GuoBofeng WangZhuo HanSiqi WuJiafeng LiuHuaxing HuangJin ZhuFengjiao AnZesong LinKunlun MoJieying TanChunqiao LiuLi WangXin DengGuigang LiJianping JiHong OuyangPublished in: Nature communications (2024)
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.
Keyphrases
- single cell
- transcription factor
- rna seq
- gene expression
- genome wide
- endothelial cells
- dna methylation
- high throughput
- dna damage
- optical coherence tomography
- genome wide identification
- single molecule
- signaling pathway
- wound healing
- induced pluripotent stem cells
- living cells
- minimally invasive
- fluorescent probe
- heat shock protein