Transdifferentiation of periodontal ligament-derived stem cells into retinal ganglion-like cells and its microRNA signature

• Published in: Scientific reports Vol. 5; no. 1; p. 16429
• Main Authors: Ng, Tsz Kin, Yung, Jasmine S. Y., Choy, Kwong Wai, Cao, Di, Leung, Christopher K. S., Cheung, Herman S., Pang, Chi Pui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.11.2015; Nature Publishing Group
• Subjects: 13/100; 14/35; 14/63; 38/61; 631/337/384/331; 631/532/1360; Beta2 protein; Biomarkers; Blindness; Calcium; Calcium Signaling - drug effects; Cell Transdifferentiation; Cells, Cultured; Cluster Analysis; Computational Biology - methods; Developed countries; Gene Expression Profiling; Glutamic Acid - pharmacology; Humanities and Social Sciences; Humans; MicroRNAs; MicroRNAs - genetics; miRNA; multidisciplinary; Periodontal ligament; Periodontal Ligament - cytology; PTEN protein; Retina; Retinal Ganglion Cells - cytology; Retinal Ganglion Cells - metabolism; RNA Interference; RNA, Messenger - genetics; Science; Six3 gene; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Tau protein; Transcriptome; Tubulin; Vascular endothelial growth factor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep16429

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.