Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells
The reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) has broad applications in regenerative medicine. The generation of self-organized retinal structures from these iPSCs offers the opportunity to study retinal development and model-specific retinal disease with patient...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/7858796 |
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| author | Amélie Slembrouck-Brec Amélie Rodrigues Oriane Rabesandratana Giuliana Gagliardi Céline Nanteau Stéphane Fouquet Gilles Thuret Sacha Reichman Gael Orieux Olivier Goureau |
| author_facet | Amélie Slembrouck-Brec Amélie Rodrigues Oriane Rabesandratana Giuliana Gagliardi Céline Nanteau Stéphane Fouquet Gilles Thuret Sacha Reichman Gael Orieux Olivier Goureau |
| author_sort | Amélie Slembrouck-Brec |
| collection | DOAJ |
| description | The reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) has broad applications in regenerative medicine. The generation of self-organized retinal structures from these iPSCs offers the opportunity to study retinal development and model-specific retinal disease with patient-specific iPSCs and provides the basis for cell replacement strategies. In this study, we demonstrated that the major type of glial cells of the human retina, Müller cells, can be reprogrammed into iPSCs that acquire classical signature of pluripotent stem cells. These Müller glial cell-derived iPSCs were able to differentiate toward retinal fate and generate concomitantly retinal pigmented epithelial cells and self-forming retinal organoid structures containing retinal progenitor cells. Retinal organoids recapitulated retinal neurogenesis with differentiation of retinal progenitor cells into all retinal cell types in a sequential overlapping order. With a modified retinal maturation protocol characterized by the presence of serum and high glucose levels, our study revealed that the retinal organoids contained pseudolaminated neural retina with important features reminiscent of mature photoreceptors, both rod and cone subtypes. This advanced maturation of photoreceptors not only supports the possibility to use 3D retinal organoids for studying photoreceptor development but also offers a novel opportunity for disease modeling, particularly for inherited retinal diseases. |
| format | Article |
| id | doaj-art-028b997cd5304c089fbd690b8b3935b1 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-028b997cd5304c089fbd690b8b3935b12025-02-03T01:30:36ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/78587967858796Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal CellsAmélie Slembrouck-Brec0Amélie Rodrigues1Oriane Rabesandratana2Giuliana Gagliardi3Céline Nanteau4Stéphane Fouquet5Gilles Thuret6Sacha Reichman7Gael Orieux8Olivier Goureau9Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceBiologie, Ingénierie et Imagerie de la Greffe de Cornée, EA2521, Faculté de Médecine, Université Jean Monnet, Saint-Etienne, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, FranceThe reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) has broad applications in regenerative medicine. The generation of self-organized retinal structures from these iPSCs offers the opportunity to study retinal development and model-specific retinal disease with patient-specific iPSCs and provides the basis for cell replacement strategies. In this study, we demonstrated that the major type of glial cells of the human retina, Müller cells, can be reprogrammed into iPSCs that acquire classical signature of pluripotent stem cells. These Müller glial cell-derived iPSCs were able to differentiate toward retinal fate and generate concomitantly retinal pigmented epithelial cells and self-forming retinal organoid structures containing retinal progenitor cells. Retinal organoids recapitulated retinal neurogenesis with differentiation of retinal progenitor cells into all retinal cell types in a sequential overlapping order. With a modified retinal maturation protocol characterized by the presence of serum and high glucose levels, our study revealed that the retinal organoids contained pseudolaminated neural retina with important features reminiscent of mature photoreceptors, both rod and cone subtypes. This advanced maturation of photoreceptors not only supports the possibility to use 3D retinal organoids for studying photoreceptor development but also offers a novel opportunity for disease modeling, particularly for inherited retinal diseases.http://dx.doi.org/10.1155/2019/7858796 |
| spellingShingle | Amélie Slembrouck-Brec Amélie Rodrigues Oriane Rabesandratana Giuliana Gagliardi Céline Nanteau Stéphane Fouquet Gilles Thuret Sacha Reichman Gael Orieux Olivier Goureau Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells Stem Cells International |
| title | Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells |
| title_full | Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells |
| title_fullStr | Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells |
| title_full_unstemmed | Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells |
| title_short | Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells |
| title_sort | reprogramming of adult retinal muller glial cells into human induced pluripotent stem cells as an efficient source of retinal cells |
| url | http://dx.doi.org/10.1155/2019/7858796 |
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