title: Transdifferentiation of periodontal ligament-derived stem cells into retinal ganglion-like cells and its microRNA signature.
abstract: Retinal diseases are the leading causes of irreversible visual impairment and blindness in the developed countries. Human retina has limited regenerative power to replace cell loss. Stem cell replacement therapy has been proposed as a viable option. Previously, we have induced human adult periodontal ligament stem cells (PDLSCs) to the retinal lineage. In this study, we modified our induction protocol to direct human adult PDLSCs into retinal ganglion-like cells and determined the microRNA (miRNA) signature of this transdifferentiation process. The differentiated PDLSCs demonstrated the characteristics of functional neurons as they expressed neuronal and retinal ganglion cell markers (ATOH7, POU4F2, β-III tubulin, MAP2, TAU, NEUROD1 and SIX3), formed synapses and showed glutamate-induced calcium responses as well as spontaneous electrical activities. The global miRNA expression profiling identified 44 upregulated and 27 downregulated human miRNAs after retinal induction. Gene ontology analysis of the predicted miRNA target genes confirmed the transdifferentiation is closely related to neuronal differentiation processes. Furthermore, the expressions of 2 miRNA-targeted candidates, VEGF and PTEN, were significantly upregulated during the induction process. This study identified the transdifferentiation process of human adult stem cells into retinal ganglion-like cells and revealed the involvement of both genetic and miRNA regulatory mechanisms.
authors.affiliation: Department of Ophthalmology &Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Tsz Kin
authors.initials: TK
authors.lastname: Ng
authors.affiliation: Department of Ophthalmology &Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jasmine S Y
authors.initials: JS
authors.lastname: Yung
authors.affiliation: Department of Obstetrics &Gynaecology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.affiliation: Department of Ophthalmology &Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Di
authors.initials: D
authors.lastname: Cao
authors.affiliation: Department of Ophthalmology &Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Christopher K S
authors.initials: CK
authors.lastname: Leung
authors.affiliation: Geriatric Research, Education and Clinical Center, Miami Veterans Affairs Medical Center, Miami, FL, United States.|Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL, United States.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Cheung
authors.affiliation: Department of Ophthalmology &Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D015415:Biomarkers; D020013:Calcium Signaling / Q000187:drug effects; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010513:Periodontal Ligament / Q000166:cytology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012333:RNA, Messenger; D018698:Glutamic Acid