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Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution
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Abstract
Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable "developed" state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.
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“ABCA4 is also present at extremely low levels in the retinal pigment epithelium (RPE) where it has been proposed to enhance endolysosomal function (2, 3).”
From Retinal gene therapy for Stargardt disease with dual AAV intein vectors is both safe and effective in large animal models (2025) · cites this paper as [2]
Experimental — accuracy not yet measuredIn the citing paper
“The physiological similarities between human and macaque retina (Cowan et al., 2019; Kling et al., 2020; Soto et al., 2020; Rodieck, 1998), including their responses to electrical stimulation (Madugula et al., 2022), suggest that the benefits of the present stimulation approach could translate from the ex vivo lab prototype with healthy macaque retina to an in vivo implant in the degenerated human”
From Precise control of neural activity using dynamically optimized electrical stimulation (2024) · cites this paper as Cowan et al., 2019
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Metadata
- Authors
- Cowan, C. S., Renner, M., De Gennaro, M., Gross-Scherf, B., Goldblum, D., Hou, Y., Munz, M., Rodrigues, T. M., Krol, J., Szikra, T., Cuttat, R., Waldt, A., Papasaikas, P., Diggelmann, R., Patino-Alvarez, C. P., Galliker, P., Spirig, S. E., Pavlinic, D., Gerber-Hollbach, N., Schuierer, S., Srdanovic, A., Balogh, M., Panero, R., Kusnyerik, A., Szabo, A., Stadler, M. B., Orgül, S., Picelli, S., Hasler, P. W., Hierlemann, A., Scholl, H. P. N., Roma, G., Nigsch, F., & Roska, B.
- Affiliations
- Institute of Molecular and Clinical Ophthalmology Basel (CH)
- University of Basel (CH)
- Novartis Institutes for BioMedical Research (CH)
- SIB Swiss Institute of Bioinformatics (CH)
- ETH Zurich (CH)
- Friedrich Miescher Institute (CH)
- Johns Hopkins University (US)
- Novartis (Switzerland) (CH)
- Corresponding author
- Roma, Guglielmo
- Nigsch, Florian
- Roska, Botond
- ORCID
- Cowan, Cameron S.
- Renner, Magdalena
- Goldblum, David
- Hou, Yanyan
- Munz, Martin
- Rodrigues, Tiago M.
- Cuttat, Rachel
- Waldt, Annick
- Papasaikas, Panagiotis
- Diggelmann, Roland
- Spirig, Stefan E.
- Schuierer, Sven
- Srdanovic, Aldin
- Panero, Riccardo
- Stadler, Michael B.
- Orgül, Selim
- Picelli, Simone
- Hasler, Pascal W.
- Hierlemann, Andreas
- Scholl, Hendrik P.N.
- Roma, Guglielmo
- Nigsch, Florian
- Roska, Botond
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 182
- Issue
- 6
- Pages
- 1623-1640.e34
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7505495
- OpenAlex
- W3087102910
- Cited by
- 654
- References
- 94
- Citations by year
- 2026: 79 · 2025: 118 · 2024: 118 · 2023: 113 · 2022: 123 · 2021: 74 · 2020: 23
- FWCI
- 26.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- The Novartis Repository (Novartis) (submittedVersion, cc-by)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection (cc-by)
- Funders
- European Research Council
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- retinal cell types, single-cell transcriptomics, retinal development, photosensitivity, retinal pigment epithelium, choroid, fovea, macular degeneration, cell type specificity, retinal repair
- MeSH terms
- Cell Differentiation, Cell Line, Electrophysiology, Female, Multigene Family, Humans, Microscopy, Electron, Naphthoquinones, Organoids, Retina, Synapses, In Situ Hybridization, Gene Expression Regulation, Developmental, Cell Culture Techniques, Genetic Predisposition to Disease, Induced Pluripotent Stem Cells, Single-Cell Analysis, Transcriptome
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