title: Discovery of molecular markers to discriminate corneal endothelial cells in the human body.
abstract: The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant number of CECs results in corneal edema called bullous keratopathy which can lead to severe visual loss. Corneal transplantation is the most effective method to treat corneal endothelial dysfunction, where it suffers from donor shortage. Therefore, regeneration of CECs from other cell types attracts increasing interests, and specific markers of CECs are crucial to identify actual CECs. However, the currently used markers are far from satisfactory because of their non-specific expression in other cell types. Here, we explored molecular markers to discriminate CECs from other cell types in the human body by integrating the published RNA-seq data of CECs and the FANTOM5 atlas representing diverse range of cell types based on expression patterns. We identified five genes, CLRN1, MRGPRX3, HTR1D, GRIP1 and ZP4 as novel markers of CECs, and the specificities of these genes were successfully confirmed by independent experiments at both the RNA and protein levels. Notably none of them have been documented in the context of CEC function. These markers could be useful for the purification of actual CECs, and also available for the evaluation of the products derived from other cell types. Our results demonstrate an effective approach to identify molecular markers for CECs and open the door for the regeneration of CECs in vitro.
authors: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, Japan.
authors: Masahito
authors: M
authors: Yoshihara
authors: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, Japan; Preventive Medicine and Applied Genomics Unit, RIKEN Advanced Center for Computing and Communication, Yokohama, Kanagawa, Japan.
authors: Hiroko
authors: H
authors: Ohmiya
authors: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Susumu
authors: S
authors: Hara
authors: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Satoshi
authors: S
authors: Kawasaki
authors: RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan.
authors: Yoshihide
authors: Y
authors: Hayashizaki
authors: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan.
authors: Masayoshi
authors: M
authors: Itoh
authors: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, Japan; Preventive Medicine and Applied Genomics Unit, RIKEN Advanced Center for Computing and Communication, Yokohama, Kanagawa, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan.
authors: Hideya
authors: H
authors: Kawaji
authors: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Motokazu
authors: M
authors: Tsujikawa
authors: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Kohji
authors: K
authors: Nishida
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D016039:Corneal Transplantation / Q000379:methods; D004527:Egg Proteins / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004728:Endothelium, Corneal / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods; D000072216:Zona Pellucida Glycoproteins
chemical_list: D015415:Biomarkers; C437067:CLRN1 protein, human; D002352:Carrier Proteins; D004527:Egg Proteins; C491310:GRIP1 protein, human; C501064:MRGPRX3 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D044346:Receptor, Serotonin, 5-HT1D; D043562:Receptors, G-Protein-Coupled; C082833:ZP4 protein, human; D000072216:Zona Pellucida Glycoproteins