Deciphering cell fates of the human cornea with a multi‐omics meta atlas

Abstract

The human cornea is a transparent tissue composed of several layers that allow light to enter the eye. Disruption of the function of various cells in different layers can give rise to diseases that affect the transparency of the cornea. Understanding the precise cell fates of the cornea and the underlying molecular mechanisms is pivotal for dissecting the pathology of corneal diseases and exploring treatments and regeneration. Currently, there is a lack of a precise cell fate map for the human cornea. In this study, we constructed a multi‐omics meta‐atlas to define cell fates in the human adult and embryonic cornea, by integrating publicly available datasets. This multi‐omics meta‐atlas is comprised of RNA‐seq data representing genome‐wide gene expression profiles and ATAC‐seq data annotating regulatory genomic regions that control gene expression in single‐cells of the cornea. We identified the key transcription factors and combinations that determine cell fates in the human cornea, with gene regulatory network analyses using the meta‐atlas. Some of these transcription factors are functionally validated. We also applied this meta‐atlas to analyse single cells of the cornea derived from keratoconus patients and showed an expansion of corneal stromal stem cells as a potential disease mechanism. In conclusion, this study provides an extensive reference of cell fates of the human cornea that can be used to dissect disease mechanisms. This meta‐atlas also provides insights for therapeutic discovery and molecular blueprints for corneal regeneration.