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.
