Abstract
Corneal endothelial cells (CECs) are essential for maintaining the clarity of the cornea. Because CECs have limited proliferative ability, interest is growing in their potentially therapeutic regeneration from pluripotent stem cells. However, the molecular mechanisms of human CEC differentiation remain largely unknown. To determine the key regulators of CEC characteristics, here we generated a comprehensive promoter-level expression profile of human CECs, using cap analysis of gene expression (CAGE) with a single molecule sequencer. Integration with the FANTOM5 promoter-level expression atlas, which includes transcriptome profiles of various human tissues and cells, enabled us to identify 45 promoters at 28 gene loci that are specifically expressed in CECs. We further discovered that the expression of transcription factor POU class 6 homeobox 2 (POU6F2) is restricted to CECs, and upregulated during human CEC differentiation, suggesting that POU6F2 is pivotal to terminal differentiation of CECs. These CEC-specific promoters would be useful for the assessment of fully differentiated CECs derived from pluripotent stem cells. These findings promote the development of corneal regenerative medicine.
Highlights
Cornea is a transparent, avascular tissue located at the front of the eye
After a careful quality check and elimination of inadequate data, we identified 137 and 206 promoters that were strictly specific to corneal endothelial (CE) tissues and cultured corneal endothelial cell (CEC), respectively
45 promoters at 28 gene loci were expressed in both CE tissues and cultured CECs
Summary
Avascular tissue located at the front of the eye. Corneal endothelium is the innermost monolayer of the cornea attached to Descemet's membrane. Corneal endothelial cells (CECs) play a crucial role in the maintenance of corneal transparency, by controlling the movement of ions and water between the corneal stroma and the anterior chamber (Hodson and Miller, 1976; Maurice, 1972). Because human CECs have limited proliferative ability (Joyce et al, 1996), significant loss of CECs due to disease or trauma can cause corneal edema, corneal opacification, and, impaired vision. Allogeneic corneal transplantation is the most effective way to treat
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