TY - JOUR
KW - Cell Culture Techniques
KW - Cell Differentiation
KW - Cell Line
KW - Electrophysiology
KW - Female
KW - Gene Expression Regulation, Developmental
KW - Genetic Predisposition to Disease
KW - Humans
KW - In Situ Hybridization
KW - induced pluripotent stem cells
KW - Microscopy, Electron
KW - Multigene Family
KW - Naphthoquinones
KW - organoids
KW - Retina
KW - Single-Cell Analysis
KW - Synapses
KW - Transcriptome
KW - eye disease
KW - human retina
KW - macular degeneration
KW - organoid
KW - organoid development
KW - Retina
KW - retinal organoid
KW - single cell sequencing
KW - synaptic function
KW - Transcriptome
AU - Cameron S. Cowan
AU - Magdalena Renner
AU - Martina De Gennaro
AU - Brigitte Gross-Scherf
AU - David Goldblum
AU - Yanyan Hou
AU - Martin Munz
AU - Tiago M. Rodrigues
AU - Jacek Krol
AU - Tamas Szikra
AU - Rachel Cuttat
AU - Annick Waldt
AU - Panagiotis Papasaikas
AU - Roland Diggelmann
AU - Claudia P. Patino-Alvarez
AU - Patricia Galliker
AU - Stefan E. Spirig
AU - Dinko Pavlinic
AU - Nadine Gerber-Hollbach
AU - Sven Schuierer
AU - Aldin Srdanovic
AU - Marton Balogh
AU - Riccardo Panero
AU - Akos Kusnyerik
AU - Arnold Szabo
AU - Michael B. Stadler
AU - Selim Orgül
AU - Simone Picelli
AU - Pascal W. Hasler
AU - Andreas Hierlemann
AU - Hendrik P. N. Scholl
AU - Guglielmo Roma
AU - Florian Nigsch
AU - Botond Roska
AB - 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.
BT - Cell
DA - 2020-09-17
DO - 10.1016/j.cell.2020.08.013
IS - 6
LA - eng
N2 - 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.
PY - 2020
SP - 1623
EP - 1640.e34
T2 - Cell
TI - Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution
VL - 182
SN - 1097-4172
ER -