Core transcription regulatory circuitry orchestrates corneal epithelial homeostasis
Resource: State Key Laboratory of Ophthalmology
Written by: State Key Laboratory of Ophthalmology
Proofread by: Jiawei Wang
Edited by: Xianjing Wei
The corneal epithelium is a barrier structure of the ocular dioptric system, and its integrity and homeostasis are essential for a clear vision. The self-renewal and regeneration of the corneal epithelium are sustained by a population of limbal stem/progenitor cells (LSCs), which are segregated in the basal layer of the limbal zone of the peripheral cornea. LSC deficiency or dysfunction causes corneal blindness characterized by opacification, neovascularization, conjunctivalization of the cornea, and disorganized corneal stroma. The identity, lineage commitment and plasticity of mammalian adult stem cells are orchestrated by synergistic interaction between transcription factors (TFs) and lineage-restricted epigenetic landscape. To data, the critical regulators of LSCs and how the TF cooperativity underlies LSC identity and homeostasis via establishing specific epigenetic architecture are largely unknown. The team of Prof. Yizhi Liu and Hong Ouyang from State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center delineates super-enhancer and chromatin accessibility landscapes of LSCs and finds that RUNX1 and SMAD3 are required for maintenance of corneal epithelial identity and homeostasis. RUNX1, PAX6, and SMAD3 (RPS) interact with each other and synergistically establish a core transcription regulatory circuitry (CRC) to govern the lineage-specific cis-regulatory atlas. Disturbance of RPS cooperation results in cell identity switching and dysfunction of the corneal epithelium, which is strongly linked to various human corneal diseases. Their work highlights the CRC TF-mediated regulatory networks for stratified epithelial homeostasis and pathogenesis.
At the beginning of 2021, their latest research work, entitled "Core transcription regulatory circuitry orchestrates corneal epithelial homeostasis" was published online in Nature Communications, the sub journal of Nature. This study was funded by the National Key Research and Development (R&D) Program of China, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, and the Guangdong Innovative and Entrepreneurial Research Team Program. Ph.D. student Mingsen Li is the first author, Prof. Yizhi Liu and Hong Ouyang are the corresponding authors.