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Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5
Human retinal organoids from induced pluripotent stem cells (hiPSCs) can be used to confirm the localization of proteins in retinal cell types and to test transduction and expression patterns of gene therapy vectors. Here, we compared the onset of CRB protein expression in human fetal retina with hu...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522954/ https://www.ncbi.nlm.nih.gov/pubmed/30956116 http://dx.doi.org/10.1016/j.stemcr.2019.03.002 |
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author | Quinn, Peter M. Buck, Thilo M. Mulder, Aat A. Ohonin, Charlotte Alves, C. Henrique Vos, Rogier M. Bialecka, Monika van Herwaarden, Tessa van Dijk, Elon H.C. Talib, Mays Freund, Christian Mikkers, Harald M.M. Hoeben, Rob C. Goumans, Marie-José Boon, Camiel J.F. Koster, Abraham J. Chuva de Sousa Lopes, Susana M. Jost, Carolina R. Wijnholds, Jan |
author_facet | Quinn, Peter M. Buck, Thilo M. Mulder, Aat A. Ohonin, Charlotte Alves, C. Henrique Vos, Rogier M. Bialecka, Monika van Herwaarden, Tessa van Dijk, Elon H.C. Talib, Mays Freund, Christian Mikkers, Harald M.M. Hoeben, Rob C. Goumans, Marie-José Boon, Camiel J.F. Koster, Abraham J. Chuva de Sousa Lopes, Susana M. Jost, Carolina R. Wijnholds, Jan |
author_sort | Quinn, Peter M. |
collection | PubMed |
description | Human retinal organoids from induced pluripotent stem cells (hiPSCs) can be used to confirm the localization of proteins in retinal cell types and to test transduction and expression patterns of gene therapy vectors. Here, we compared the onset of CRB protein expression in human fetal retina with human iPSC-derived retinal organoids. We show that CRB2 protein precedes the expression of CRB1 in the developing human retina. Our data suggest the presence of CRB1 and CRB2 in human photoreceptors and Müller glial cells. Thus the fetal CRB complex formation is replicated in hiPSC-derived retina. CRB1 patient iPSC retinal organoids showed disruptions at the outer limiting membrane as found in Crb1 mutant mice. Furthermore, AAV serotype 5 (AAV5) is potent in infecting human Müller glial cells and photoreceptors in hiPSC-derived retinas and retinal explants. Our data suggest that human photoreceptors can be efficiently transduced by AAVs in the presence of photoreceptor segments. |
format | Online Article Text |
id | pubmed-6522954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-65229542019-05-24 Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5 Quinn, Peter M. Buck, Thilo M. Mulder, Aat A. Ohonin, Charlotte Alves, C. Henrique Vos, Rogier M. Bialecka, Monika van Herwaarden, Tessa van Dijk, Elon H.C. Talib, Mays Freund, Christian Mikkers, Harald M.M. Hoeben, Rob C. Goumans, Marie-José Boon, Camiel J.F. Koster, Abraham J. Chuva de Sousa Lopes, Susana M. Jost, Carolina R. Wijnholds, Jan Stem Cell Reports Article Human retinal organoids from induced pluripotent stem cells (hiPSCs) can be used to confirm the localization of proteins in retinal cell types and to test transduction and expression patterns of gene therapy vectors. Here, we compared the onset of CRB protein expression in human fetal retina with human iPSC-derived retinal organoids. We show that CRB2 protein precedes the expression of CRB1 in the developing human retina. Our data suggest the presence of CRB1 and CRB2 in human photoreceptors and Müller glial cells. Thus the fetal CRB complex formation is replicated in hiPSC-derived retina. CRB1 patient iPSC retinal organoids showed disruptions at the outer limiting membrane as found in Crb1 mutant mice. Furthermore, AAV serotype 5 (AAV5) is potent in infecting human Müller glial cells and photoreceptors in hiPSC-derived retinas and retinal explants. Our data suggest that human photoreceptors can be efficiently transduced by AAVs in the presence of photoreceptor segments. Elsevier 2019-04-04 /pmc/articles/PMC6522954/ /pubmed/30956116 http://dx.doi.org/10.1016/j.stemcr.2019.03.002 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Quinn, Peter M. Buck, Thilo M. Mulder, Aat A. Ohonin, Charlotte Alves, C. Henrique Vos, Rogier M. Bialecka, Monika van Herwaarden, Tessa van Dijk, Elon H.C. Talib, Mays Freund, Christian Mikkers, Harald M.M. Hoeben, Rob C. Goumans, Marie-José Boon, Camiel J.F. Koster, Abraham J. Chuva de Sousa Lopes, Susana M. Jost, Carolina R. Wijnholds, Jan Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5 |
title | Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5 |
title_full | Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5 |
title_fullStr | Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5 |
title_full_unstemmed | Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5 |
title_short | Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5 |
title_sort | human ipsc-derived retinas recapitulate the fetal crb1 crb2 complex formation and demonstrate that photoreceptors and müller glia are targets of aav5 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522954/ https://www.ncbi.nlm.nih.gov/pubmed/30956116 http://dx.doi.org/10.1016/j.stemcr.2019.03.002 |
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