title: Induction of retinal ganglion-like cells from fibroblasts by adenoviral gene delivery.
abstract: Central nervous system neurons fail to regenerate after birth, which greatly hampers the effective treatment of many neurodegenerative diseases. Neurons differentiated from induced pluripotent stem cells have been considered a possible option for cell-based therapies. Recent discoveries have revealed that fibroblasts can be directly converted into neurons without a transition through a pluripotent state. This approach might serve as a more efficient and convenient method for the cellular therapy of neurodegenerative diseases. Currently, several types of neurons have been directly generated from fibroblasts, including dopamine neurons, motor neurons and neural progenitor cells. In our study, by screening a series of candidate genes, we found that the adenovirus-mediated transduction of Ascl1, Brn3b and Ngn2 can directly convert mouse fibroblasts to retinal ganglion-like cells. The induced retinal ganglion-like cells co-express multiple retinal ganglion cell markers, and exhibit membrane properties of functional neurons. The reprogramming mediated by adenoviruses occurs much sooner than that mediated by lentiviruses. Furthermore, the induced retinal ganglion-like cells that are produced via adenoviral gene delivery are free of exogenous gene integration. Retinal ganglion-like cells that are induced by adenoviruses demonstrate great potential applicability in clinical therapy and provide a novel platform for the research of retinal degenerative diseases.
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200032, China.
authors.forename: F
authors.initials: F
authors.lastname: Meng
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Gu
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Guo
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D055724:Electrophysiological Phenomena / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D018014:Gene Transfer Techniques; D051379:Mice; D016133:Polymerase Chain Reaction; D061251:Primary Cell Culture; D012165:Retinal Ganglion Cells / Q000502:physiology*; D014157:Transcription Factors
chemical_list: D014157:Transcription Factors
keywords: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; AB(2)N-iNs; AB(2)N-induced neurons; EGTA; ESCs; ETF; HEPES; MEF; MOI; PCR; RGC; adenovirus; ear tip fibroblast; embryonic stem cells; ethylene glycol tetraacetic acid; fibroblast; iPSC; iRG-like cell; induced pluripotent stem cell; induced retinal ganglion-like cell; mouse embryonic fibroblast; multiplicities of infection; polymerase chain reaction; reprogramming; retinal ganglion cell