title: Maximizing functional photoreceptor differentiation from adult human retinal stem cells.
abstract: Retinal stem cells (RSCs) are present in the ciliary margin of the adult human eye and can give rise to all retinal cell types. Here we show that modulation of retinal transcription factor gene expression in human RSCs greatly enriches photoreceptor progeny, and that strong enrichment was obtained with the combined transduction of OTX2 and CRX together with the modulation of CHX10. When these genetically modified human RSC progeny are transplanted into mouse eyes, their retinal integration and differentiation is superior to unmodified RSC progeny. Moreover, electrophysiologic and behavioral tests show that these transplanted cells promote functional recovery in transducin mutant mice. This study suggests that gene modulation in human RSCs may provide a source of photoreceptor cells for the treatment of photoreceptor disease.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. tinoue@ophthal.med.osaka-u.ac.jp
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Brenda L K
authors.initials: BL
authors.lastname: Coles
authors.forename: Kim
authors.initials: K
authors.lastname: Dorval
authors.forename: Rod
authors.initials: R
authors.lastname: Bremner
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Bessho
authors.forename: Ryoichiro
authors.initials: R
authors.lastname: Kageyama
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Hino
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Craft
authors.forename: Roderick R
authors.initials: RR
authors.lastname: McInnes
authors.forename: Francois
authors.initials: F
authors.lastname: Tremblay
authors.forename: Glen T
authors.initials: GT
authors.lastname: Prusky
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics; D006085:Graft Survival / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D051857:Otx Transcription Factors / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology* / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D015293:Transducin / Q000235:genetics; D014161:Transduction, Genetic / Q000379:methods; D014162:Transfection / Q000379:methods; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; C109288:cone rod homeobox protein; D015293:Transducin