Cited by 666Retinal Development and DisordersSingle-cell and spatial transcriptomicsRetinal Diseases and Treatments

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. +26 more·2020·Cell

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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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Crossref · 10.1016/j.cell.2020.08.013

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  • ABCA4 is also present at extremely low levels in the retinal pigment epithelium, where it has been proposed to enhance endolysosomal function.

    “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]

    The Results section (Figure S7; page unavailable in our copy) reports ABCA4 expression and transcript counts in retinal pigment epithelial cells. It does not establish that the levels are extremely low or propose that ABCA4 enhances endolysosomal function. (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • The physiological similarities between human and macaque retina, including their responses to electrical stimulation, 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 retina.

    “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”

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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
Venue
Cell
Publisher
Elsevier BV
Published
2020-09
Volume
182
Issue
6
Pages
1623-1640.e34
ISSN
0092-8674 (ISSN-L)
OpenAlex
W3087102910
Cited by
654
References
94
Citations by year
2026: 79 · 2025: 118 · 2024: 118 · 2023: 113 · 2022: 123 · 2021: 74 · 2020: 23 · 2019: 5 · 2012: 1
FWCI
26.98
Type
journal article
Language
en
Open access
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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