Retinal organoids from pluripotent stem cells efficiently recapitulate retinogenesis
Open accessAbstract
The plasticity of pluripotent stem cells provides new possibilities for studying development, degeneration, and regeneration. Protocols for the differentiation of retinal organoids from embryonic stem cells have been developed, which either recapitulate complete eyecup morphogenesis or maximize photoreceptor genesis. Here, we have developed a protocol for the efficient generation of large, 3D-stratified retinal organoids that does not require evagination of optic-vesicle-like structures, which so far limited the organoid yield. Analysis of gene expression in individual organoids, cell birthdating, and interorganoid variation indicate efficient, reproducible, and temporally regulated retinogenesis. Comparative analysis of a transgenic reporter for PAX6, a master regulator of retinogenesis, shows expression in similar cell types in mouse in vivo, and in mouse and human retinal organoids. Early or late Notch signaling inhibition forces cell differentiation, generating organoids enriched with cone or rod photoreceptors, respectively, demonstrating the power of our improved organoid system for future research in stem cell biology and regenerative medicine.
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Cell line variability is a commonly cited shortcoming of organoid systems that rely on tissue self-assembly.
“Cell line variability is a commonly cited shortcoming of organoid systems that rely on tissue self-assembly (Chen et al., 2014; Völkner et al., 2016).”
From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Völkner et al., 2016
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- Authors
- Völkner, M., Zschätzsch, M., Rostovskaya, M., Overall, R. W., Busskamp, V., Anastassiadis, K., & Karl, M. O.
- Affiliations
- German Center for Neurodegenerative Diseases (DZNE) Dresden (DE)
- Biotechnologisches Zentrum (DE)
- Center for Regenerative Therapies Dresden (DE)
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 6
- Issue
- 4
- Pages
- 525-538
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC4834051
- OpenAlex
- W2319627288
- Cited by
- 273
- References
- 0
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 13 · 2023: 31 · 2022: 36 · 2021: 37 · 2020: 29 · 2019: 30 · 2018: 26 · 2017: 28 · 2016: 7
- FWCI
- 15.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DZNE Pub (submittedVersion, cc-by-nc-nd)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc)
- Apollo
- Funders
- DZNE Helmholtz
- TU Dresden CRTD
- DFG
- MedDrive TU Dresden UKD-Medical Faculty
- Novartis Pharma GmbH
- Volkswagen Foundation Freigeist
- ESTOOLS
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- retinal organoids, retinal development, pluripotent stem cells, embryonic stem cells, photoreceptor differentiation, Notch signaling inhibition, cone photoreceptors, rod photoreceptors, retinal regeneration
- MeSH terms
- Human Embryonic Stem Cells, Mouse Embryonic Stem Cells, PAX6 Transcription Factor, Animals, Cell Differentiation, Cells, Cultured, Humans, Mice, Transgenic, Organ Culture Techniques, Organoids, Retina, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Organogenesis, Pluripotent Stem Cells, Mice
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