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

Summary

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.

Graphical Abstract

Highlights

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  Light-sensitive, multilayered human retinal organoids with functional synapses

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  285,441 transcriptomes from light-responsive human retinas and retinal organoids

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  Organoid cell types converge to adult peripheral retinal cell types

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  Linking retinal diseases to human retinal and retinal organoid cell types

Abstract

Light-sensitive, multilayered human retinal organoids with functional synapses are developed and benchmarked against human retinas obtained under conditions that preserve retinal integrity.