Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration.
- Kruczek K Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Gonzalez-Cordero A Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Goh D Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Naeem A Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Jonikas M Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Blackford SJI Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Kloc M Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Duran Y Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Georgiadis A Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Sampson RD Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Maswood RN Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Smith AJ Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Decembrini S Department of Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, 1004 Lausanne, Switzerland.
- Arsenijevic Y Department of Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, 1004 Lausanne, Switzerland.
- Sowden JC Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
- Pearson RA Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- West EL Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
- Ali RR Department of Genetics, UCL Institute of Ophthalmology, London EC1V 9EL, UK; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, City Road, London EC1V 2PD, UK. Electronic address: r.ali@ucl.ac.uk.
- 2017-05-30
Published in:
- Stem cell reports. - 2017
blindness
cell- and tissue-based therapy
mouse embryonic stem cells
retina
retinal cone photoreceptor cells
retinal degeneration
Adaptor Proteins, Signal Transducing
Animals
Basic-Leucine Zipper Transcription Factors
Cell Differentiation
Disease Models, Animal
Eye Proteins
Hepatocyte Nuclear Factor 6
Leukemia Inhibitory Factor
Mice
Mice, Knockout
Mouse Embryonic Stem Cells
Oligodendrocyte Transcription Factor 2
Opsins
Orphan Nuclear Receptors
Otx Transcription Factors
RNA Interference
RNA, Small Interfering
Receptors, Notch
Retinal Cone Photoreceptor Cells
Retinal Degeneration
Signal Transduction
Tretinoin
English
The loss of cone photoreceptors that mediate daylight vision represents a leading cause of blindness, for which cell replacement by transplantation offers a promising treatment strategy. Here, we characterize cone differentiation in retinas derived from mouse embryonic stem cells (mESCs). Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive precursors and, subsequently, photoreceptors exhibiting cone-specific phototransduction-related proteins. We establish that stage-specific inhibition of the Notch pathway increases cone cell differentiation, while retinoic acid signaling regulates cone maturation, comparable with their actions in vivo. MESC-derived cones can be isolated in large numbers and transplanted into adult mouse eyes, showing capacity to survive and mature in the subretinal space of Aipl1-/- mice, a model of end-stage retinal degeneration. Together, this work identifies a robust, renewable cell source for cone replacement by purified cell suspension transplantation.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1016/j.stemcr.2017.04.030
- PMID 28552606
- Persistent URL
- https://sonar.ch/global/documents/106167
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