title: Identification of novel molecular markers through transcriptomic analysis in human fetal and adult corneal endothelial cells.
abstract: The corneal endothelium is composed of a monolayer of corneal endothelial cells (CECs), which is essential for maintaining corneal transparency. To better characterize CECs in different developmental stages, we profiled mRNA transcriptomes in human fetal and adult corneal endothelium with the goal to identify novel molecular markers in these cells. By comparing CECs with 12 other tissue types, we identified 245 and 284 signature genes that are highly expressed in fetal and adult CECs, respectively. Functionally, these genes are enriched in pathways characteristic of CECs, including inorganic anion transmembrane transporter, extracellular matrix structural constituent and cyclin-dependent protein kinase inhibitor activity. Importantly, several of these genes are disease target genes in hereditary corneal dystrophies, consistent with their functional significance in CEC physiology. We also identified stage-specific markers associated with CEC development, such as specific members in the transforming growth factor beta and Wnt signaling pathways only expressed in fetal, but not in adult CECs. Lastly, by the immunohistochemistry of ocular tissues, we demonstrated the unique protein localization for Wnt5a, S100A4, S100A6 and IER3, the four novel markers for fetal and adult CECs. The identification of a new panel of stage-specific markers for CECs would be very useful for characterizing CECs derived from stem cells or ex vivo expansion for cell replacement therapy.
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Chen
authors.forename: Kevin
authors.initials: K
authors.lastname: Huang
authors.forename: Martin N
authors.initials: MN
authors.lastname: Nakatsu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xue
authors.forename: Sophie X
authors.initials: SX
authors.lastname: Deng
authors.forename: Guoping
authors.initials: G
authors.lastname: Fan
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004728:Endothelium, Corneal / Q000166:cytology*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D005136:Eye Proteins; C099815:IER3 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D009418:S100 Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein