title: Generation of Functional Human Retinal Ganglion Cells with Target Specificity from Pluripotent Stem Cells by Chemically Defined Recapitulation of Developmental Mechanism.
abstract: Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) lead to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, that is, the embryonic stem cells and induced pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific, chemically defined protocol that selectively generates RGCs across species, including human, by recapitulating the developmental mechanism. The de novo generated RGCs from pluripotent cells are similar to native RGCs at the molecular, biochemical, functional levels. They also express axon guidance molecules, and discriminate between specific and nonspecific targets, and are nontumorigenic. Stem Cells 2017;35:572-585.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Teotia
authors.affiliation: Department of Pharmacology, Creighton University, Omaha, Nebraska, USA.
authors.forename: Divyan A
authors.initials: DA
authors.lastname: Chopra
authors.affiliation: Department of Pharmacology, Creighton University, Omaha, Nebraska, USA.
authors.forename: Shashank Manohar
authors.initials: SM
authors.lastname: Dravid
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Van Hook
authors.affiliation: Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: John
authors.initials: J
authors.lastname: Morrison
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Angie
authors.initials: A
authors.lastname: Rizzino
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D003470:Culture Media; D055724:Electrophysiological Phenomena; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005809:Genes, Regulator; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D012097:Repressor Proteins / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D000099229:RE1-Silencing Transcription Factor
chemical_list: D003470:Culture Media; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor
keywords: Chemically defined medium; Directed differentiation; Embryonic stem cells; Glaucoma; Induced pluripotent stem cells; Retinal ganglion cells