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.

概述细胞类多样性及其靶器官功能的人类器官对于基础和翻译研究具有重要意义。我们开发了具有多个核和突触层以及功能性突触的光敏性人类视网膜类器官。我们在七个发育时间点从这些类器官以及从光响应的成年人类视网膜的外围，中央凹，色素上皮和脉络膜对285,441个单细胞的RNA进行了测序，并进行了组织化学分析。在成熟的组织体细胞类型在体外以稳定的“发达”国家在类似人类视网膜发育的速度在体内。类器官细胞类型的转录组趋于成年外周视网膜细胞类型的转录组。疾病相关基因的表达在成年视网膜中是细胞类型特异性的，而在类器官中则保留了细胞类型的特异性。我们将意外的细胞类型包含在黄斑变性等疾病中。该资源确定了用于研究类器官的疾病机理和人类视网膜靶向修复的细胞靶标。