Publication Date:
2016-03-10
Description:
The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, Ryuhei -- Ishikawa, Yuki -- Sasamoto, Yuzuru -- Katori, Ryosuke -- Nomura, Naoki -- Ichikawa, Tatsuya -- Araki, Saori -- Soma, Takeshi -- Kawasaki, Satoshi -- Sekiguchi, Kiyotoshi -- Quantock, Andrew J -- Tsujikawa, Motokazu -- Nishida, Kohji -- England -- Nature. 2016 Mar 17;531(7594):376-80. doi: 10.1038/nature17000. Epub 2016 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. ; Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. ; Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan. ; Structural Biophysics Group, School of Optometry and Vision Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF24 4HQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26958835" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Lineage
;
Cornea/*cytology/*growth & development/physiology
;
Corneal Transplantation
;
Ectoderm/cytology
;
Epithelial Cells/cytology
;
Epithelium, Corneal/cytology
;
Female
;
Humans
;
Induced Pluripotent Stem Cells/*cytology
;
Lens, Crystalline/cytology
;
Mice
;
Morphogenesis
;
Phenotype
;
Rabbits
;
*Recovery of Function
;
Retinal Pigment Epithelium/cytology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
