03426nas a2200877   4500000000100000000000100001008004100002260001500043653002800058653002500086653001400111653002200125653001100147653004600158653003800204653001100242653002600253653003500279653002500314653002100339653002000360653001400380653001100394653002500405653001300430653001800443653001600461653001700477653002500494653001300519653002500532653001100557653002100568653002700589653002200616653001800638100002100656700002100677700002300698700002600721700001900747700001500766700001600781700002300797700001500820700001700835700001800852700001700870700002600887700002200913700003000935700002200965700002100987700001901008700002701027700001901054700002001073700001801093700002001111700001901131700001701150700002301167700001701190700001901207700002101226700002301247700002501270700001901295700001901314700001701333245007901350300001801429490000801447520107901455022001402534       2020                            d  c2020-09-1710aCell Culture Techniques10aCell Differentiation10aCell Line10aElectrophysiology10aFemale10aGene Expression Regulation, Developmental10aGenetic Predisposition to Disease10aHumans10aIn Situ Hybridization10ainduced pluripotent stem cells10aMicroscopy, Electron10aMultigene Family10aNaphthoquinones10aorganoids10aRetina10aSingle-Cell Analysis10aSynapses10aTranscriptome10aeye disease10ahuman retina10amacular degeneration10aorganoid10aorganoid development10aRetina10aretinal organoid10asingle cell sequencing10asynaptic function10aTranscriptome1 aCameron S. Cowan1 aMagdalena Renner1 aMartina De Gennaro1 aBrigitte Gross-Scherf1 aDavid Goldblum1 aYanyan Hou1 aMartin Munz1 aTiago M. Rodrigues1 aJacek Krol1 aTamas Szikra1 aRachel Cuttat1 aAnnick Waldt1 aPanagiotis Papasaikas1 aRoland Diggelmann1 aClaudia P. Patino-Alvarez1 aPatricia Galliker1 aStefan E. Spirig1 aDinko Pavlinic1 aNadine Gerber-Hollbach1 aSven Schuierer1 aAldin Srdanovic1 aMarton Balogh1 aRiccardo Panero1 aAkos Kusnyerik1 aArnold Szabo1 aMichael B. Stadler1 aSelim Orgül1 aSimone Picelli1 aPascal W. Hasler1 aAndreas Hierlemann1 aHendrik P. N. Scholl1 aGuglielmo Roma1 aFlorian Nigsch1 aBotond Roska00aCell Types of the Human Retina and Its Organoids at Single-Cell Resolution  a1623-1640.e340 v1823 aHuman 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.  a1097-4172