Restricted Presence of POU6F2 in Human Corneal Endothelial Cells Uncovered by Extension of the Promoter-level Expression Atlas
Autor: | Yoshihide Hayashizaki, Masayoshi Itoh, Masahito Yoshihara, Motokazu Tsujikawa, Kohji Nishida, Hideya Kawaji, Susumu Hara, Satoshi Kawasaki |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
CE tissue corneal endothelial tissue lcsh:Medicine Biology CEC corneal endothelial cell Regenerative medicine FANTOM Functional Annotation of Mammalian Genome General Biochemistry Genetics and Molecular Biology Transcriptome 03 medical and health sciences Gene expression Humans Regeneration Promoter Regions Genetic Induced pluripotent stem cell Transcription factor lcsh:R5-920 Endothelium Corneal lcsh:R Endothelial Cells Cell Differentiation Corneal endothelial cells Promoter General Medicine HCEPs human corneal endothelial progenitors CAGE cap analysis of gene expression Molecular biology Cap analysis gene expression Cell biology Cell-type specific marker 030104 developmental biology Gene Expression Regulation POU Domain Factors cardiovascular system Homeobox dHCEPs differentiated human corneal endothelial progenitors tpm tags per million lcsh:Medicine (General) Research Paper |
Zdroj: | EBioMedicine, Vol 25, Iss C, Pp 175-186 (2017) EBioMedicine |
ISSN: | 2352-3964 |
Popis: | 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 • We comprehensively profiled promoter-level expression of human corneal endothelial cells. • Integrative transcriptome analysis identified 28 corneal endothelial cell-specific marker genes. • POU6F2 expression is restricted to corneal endothelial cells, and upregulated during differentiation. Corneal endothelial cells (CECs) are essential for maintaining corneal transparency. Owing to the high prevalence of corneal endothelial disorders, CECs are important targets in regenerative medicine. However, it has been difficult to evaluate the final CEC products owing to the lack of appropriate CEC-specific markers. In this study, we identified 28 CEC-specific marker genes by integrative transcriptome analysis. One gene of particular interest, POU6F2, is expressed almost exclusively in CECs, and upregulated during differentiation. These markers would be useful for the assessment of CECs derived from pluripotent stem cells, and this study will facilitate the translation of corneal regenerative medicine. |
Databáze: | OpenAIRE |
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