title: Generation of functional eyes from pluripotent cells.
abstract: Pluripotent cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.
authors.affiliation: Department of Ophthalmology, State University of New York (SUNY) Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Viczian
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Solessio
authors.forename: Yung
authors.initials: Y
authors.lastname: Lyou
authors.forename: Michael E
authors.initials: ME
authors.lastname: Zuber
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D005123:Eye / Q000033:anatomy & histology / Q000166:cytology / Q000254:growth & development; D005786:Gene Expression Regulation; D006801:Humans; D009474:Neurons / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D044968:Regenerative Medicine; D012160:Retina / Q000166:cytology* / Q000254:growth & development; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D014157:Transcription Factors
references.citation: Cell Cycle. 2007 Jan 15;6(2):156-9
references.pmid: 17245127
references.citation: Cell Stem Cell. 2009 Jan 9;4(1):73-9
references.pmid: 19128794
references.citation: Dev Biol. 2001 Dec 1;240(1):77-91
references.pmid: 11784048
references.citation: Neuroreport. 2003 Jan 20;14(1):143-6
references.pmid: 12544846
references.citation: Dev Biol. 1990 Sep;141(1):149-63
references.pmid: 2390999
references.citation: Dev Dyn. 2005 Jun;233(2):562-9
references.pmid: 15778984
references.citation: Development. 1997 Feb;124(3):603-15
references.pmid: 9043075
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references.pmid: 9843981
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12769-74
references.pmid: 16908856
references.citation: Mol Vis. 2007 Jan 26;13:86-95
references.pmid: 17277735
references.citation: Int J Dev Biol. 2004;48(8-9):1003-14
references.pmid: 15558491
references.citation: Dev Genet. 1997;20(3):246-57
references.pmid: 9216064
references.citation: Int Rev Cytol. 1980;63:263-322
references.pmid: 395131
references.citation: Dev Biol. 1971 Feb;24(2):264-86
references.pmid: 5553368
references.citation: J Comp Neurol. 1976 Nov 1;170(1):33-51
references.pmid: 1086313
references.citation: J Neurobiol. 1990 Apr;21(3):427-40
references.pmid: 2351962
references.citation: Semin Cell Dev Biol. 2004 Feb;15(1):91-103
references.pmid: 15036212
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11331-6
references.pmid: 16076961
references.citation: Dev Biol. 1987 Nov;124(1):200-14
references.pmid: 3666306
references.citation: Biol Cell. 2005 May;97(5):321-37
references.pmid: 15836431
references.citation: Development. 2003 Apr;130(7):1281-94
references.pmid: 12588845
references.citation: Development. 2003 Nov;130(21):5155-67
references.pmid: 12944429
references.citation: J Exp Zool. 1996 Dec 1;276(5):335-44
references.pmid: 8972584
references.citation: Dev Growth Differ. 2008 May;50(4):245-51
references.pmid: 18366385
references.citation: Dev Biol. 1999 Aug 1;212(1):25-41
references.pmid: 10419683
references.citation: Semin Cell Dev Biol. 2006 Dec;17(6):676-85
references.pmid: 17164096
references.citation: Comp Biochem Physiol B Biochem Mol Biol. 2000 Jun;126(2):169-78
references.pmid: 10874164
references.citation: J Comp Neurol. 1980 Nov 15;194(2):319-33
references.pmid: 7440804
references.citation: Int J Dev Biol. 2004 Dec;48(10):1105-12
references.pmid: 15602696
references.citation: Trends Genet. 1992 Oct;8(10):349-55
references.pmid: 1475847
references.citation: J Embryol Exp Morphol. 1971 Aug;26(1):67-79
references.pmid: 5565078
references.citation: Science. 1978 Jan 13;199(4325):202-4
references.pmid: 619452
references.citation: J Neurophysiol. 2004 Nov;92(5):2672-84
references.pmid: 15486422
references.citation: Nat Biotechnol. 2008 Feb;26(2):215-24
references.pmid: 18246062