1. Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map
- Author
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Guglielmo Roma, Nadine Gerber-Hollbach, Brigitte Gross-Scherf, Andreas Hierlemann, Márton Balogh, Roland Diggelmann, Tamas Szikra, Yanyan Hou, Botond Roska, Claudia P. Patino-Alvarez, Simone Picelli, David Goldblum, Pascal W. Hasler, Annick Waldt, Hendrik P. N. Scholl, Patricia Galliker, Magdalena Renner, Riccardo Panero, Panagiotis Papasaikas, Selim Orgül, Cameron S. Cowan, Jacek Krol, Arnold Szabo, Michael B. Stadler, Martina De Gennaro, Tiago M. Rodrigues, Aldin Srdanovic, Florian Nigsch, Rachel Cuttat-Theurillat, Stefan E. Spirig, Dinko Pavlinic, Sven Schuierer, Martin Munz, and Akos Kusnyerik more...
- Subjects
Retina ,Cell type ,Cell ,Retinal ,Biology ,Epithelium ,eye diseases ,Cell biology ,Transcriptome ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Organoid ,medicine ,sense organs ,Gene - Abstract
SummaryHow closely human organoids recapitulate cell-type diversity and cell-type maturation of their target organs is not well understood. We developed human retinal organoids with multiple nuclear and synaptic layers. We sequenced the RNA of 158,844 single cells from these organoids at six 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 adult human retinas. more...
- Published
- 2019
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