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Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution.


ABSTRACT: 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.

SUBMITTER: Cowan CS 

PROVIDER: S-EPMC7505495 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution.

Cowan Cameron S CS   Renner Magdalena M   De Gennaro Martina M   Gross-Scherf Brigitte B   Goldblum David D   Hou Yanyan Y   Munz Martin M   Rodrigues Tiago M TM   Krol Jacek J   Szikra Tamas T   Cuttat Rachel R   Waldt Annick A   Papasaikas Panagiotis P   Diggelmann Roland R   Patino-Alvarez Claudia P CP   Galliker Patricia P   Spirig Stefan E SE   Pavlinic Dinko D   Gerber-Hollbach Nadine N   Schuierer Sven S   Srdanovic Aldin A   Balogh Marton M   Panero Riccardo R   Kusnyerik Akos A   Szabo Arnold A   Stadler Michael B MB   Orgül Selim S   Picelli Simone S   Hasler Pascal W PW   Hierlemann Andreas A   Scholl Hendrik P N HPN   Roma Guglielmo G   Nigsch Florian F   Roska Botond B  

Cell 20200901 6


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  ...[more]

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