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Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map

Cowan, Cameron and Renner, Magdalena and De Gennaro, Martina and Gross-Scherf, Brigitte and Goldblum, David and Hou, Yanyan and Munz, Martin and Rodrigues, Tiago M. and Krol, Jacek and Szikra, Tamas and Cuttat-Theurillat, Rachel and Waldt, Annick and Papasaikas, Panagiotis and Diggelmann, Roland and Patino-Alvarez, Claudia P. and Galliker, Patricia and Spirig, Stefan and Pavlinic, Dinko and Gerber-Hollbach, Nadine and Schuierer, Sven and Srdanovic, Aldin and Balogh, Marton and Panero, Riccardo and Kusnyerik, Akos and Szabo, Arnold and Stadler, Michael and Orgül, Selim and Picelli, Simone and Hasler, Pascal W. and Hierlemann, Andreas and Scholl, Hendrik P. N. and Roma, Guglielmo and Nigsch, Florian and Roska, Botond (2020) Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map. Cell, 182 (6). p. 1623. ISSN 00928674

Abstract

How closely human organoids recapitulate cell-type diversity and cell-type maturation of their target organs is not well understood. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers. We sequenced the RNA of 158,844 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 and the transcriptomes of organoid cell types converged towards the transcriptomes of adult peripheral retinal cell types. The expression of disease-associated genes was significantly 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.

Item Type: Article
Date Deposited: 27 Oct 2020 00:45
Last Modified: 27 Oct 2020 00:45
URI: https://oak.novartis.com/id/eprint/42817

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