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
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
Externí odkaz: