RT Journal Article SR Electronic T1 Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map JF bioRxiv FD Cold Spring Harbor Laboratory SP 703348 DO 10.1101/703348 A1 Cameron S. Cowan A1 Magdalena Renner A1 Brigitte Gross-Scherf A1 David Goldblum A1 Martin Munz A1 Jacek Krol A1 Tamas Szikra A1 Panagiotis Papasaikas A1 Rachel Cuttat A1 Annick Waldt A1 Roland Diggelmann A1 Claudia P. Patino-Alvarez A1 Nadine Gerber-Hollbach A1 Sven Schuierer A1 Yanyan Hou A1 Aldin Srdanovic A1 Marton Balogh A1 Riccardo Panero A1 Pascal W. Hasler A1 Akos Kusnyerik A1 Arnold Szabo A1 Michael B. Stadler A1 Selim Orgül A1 Andreas Hierlemann A1 Hendrik P. N. Scholl A1 Guglielmo Roma A1 Florian Nigsch A1 Botond Roska YR 2019 UL http://biorxiv.org/content/early/2019/07/16/703348.abstract AB How 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.