Cited by 665Retinal Development and DisordersSingle-cell and spatial transcriptomicsRetinal Diseases and Treatments

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Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution

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Cowan, Cameron S., Renner, Magdalena, De Gennaro, Martina, Gross-Scherf, Brigitte, Goldblum, David, Hou, Yanyan, Munz, Martin, Rodrigues, Tiago M., Krol, Jacek, Szikra, Tamas, Cuttat, Rachel, Waldt, Annick, Papasaikas, Panagiotis, Diggelmann, Roland, Patino-Alvarez, Claudia P., Galliker, Patricia, Spirig, Stefan E., Pavlinic, Dinko, Gerber-Hollbach, Nadine, Schuierer, Sven, Srdanovic, Aldin, Balogh, Marton, Panero, Riccardo, Kusnyerik, Akos, Szabo, Arnold, Stadler, Michael B., Orgül, Selim, Picelli, Simone, Hasler, Pascal W., Hierlemann, Andreas, Scholl, Hendrik P.N., Roma, Guglielmo, Nigsch, Florian, Roska, Botond·2020·Cell

DOI 10.1016/j.cell.2020.08.013PMC PMC7505495

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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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Additional file 8 of Retinal organoids with X-linked retinoschisis RS1 (E72K) mutation exhibit a photoreceptor developmental delay and are rescued by gene augmentation therapy
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Additional file 2 of Single-cell RNA sequencing of the retina in a model of retinitis pigmentosa reveals early responses to degeneration in rods and cones
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Additional file 2 of Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci
D’haene, E., López-Soriano, V., Martínez‐García, P. M., Kalayanamontri, S., Rey, A. D., Sousa‐Ortega, A., Naranjo, S., de Sompele, S. V., Vantomme, L., Mahieu, Q., et al. (2024) · DIGITAL.CSIC (Spanish National Research Council (CSIC)) · doi:10.6084/m9.figshare.26721990
Additional file 6 of Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci
D’haene, E., López-Soriano, V., Martínez‐García, P. M., Kalayanamontri, S., Rey, A. D., Sousa‐Ortega, A., Naranjo, S., de Sompele, S. V., Vantomme, L., Mahieu, Q., et al. (2024) · DIGITAL.CSIC (Spanish National Research Council (CSIC)) · doi:10.6084/m9.figshare.26722002
Additional file 2 of Retinal organoids with X-linked retinoschisis RS1 (E72K) mutation exhibit a photoreceptor developmental delay and are rescued by gene augmentation therapy
Duan, C., Ding, C., Sun, X., Mao, S., Liang, Y., Liu, X., Ding, X., Chen, J., & Tang, S. (2024) · Figshare · doi:10.6084/m9.figshare.26727889
Additional file 3 of Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci
D’haene, E., López-Soriano, V., Martínez‐García, P. M., Kalayanamontri, S., Rey, A. D., Sousa‐Ortega, A., Naranjo, S., de Sompele, S. V., Vantomme, L., Mahieu, Q., et al. (2024) · DIGITAL.CSIC (Spanish National Research Council (CSIC)) · doi:10.6084/m9.figshare.26721993
Additional file 14 of Single-cell RNA sequencing of the retina in a model of retinitis pigmentosa reveals early responses to degeneration in rods and cones
Karademir, D., Todorova, V., Ebner, L. J. A., Samardzija, M., & Grimm, C. (2022) · Figshare · doi:10.6084/m9.figshare.19588632

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)
DOI: 10.1016/j.cell.2020.08.013
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
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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