Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland.
Cell. 2020 Sep 17;182(6):1623-1640.e34. doi: 10.1016/j.cell.2020.08.013.
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.
人类类器官能够重现其目标器官的细胞类型多样性和功能，对于基础研究和转化研究具有重要价值。我们开发了具有多层核和突触以及功能性突触的光敏感人类视网膜类器官。我们对来自这些类器官的 285441 个单细胞进行了 RNA 测序，这些类器官在七个发育时间点和对光反应的成人人类视网膜的周边、黄斑、色素上皮和脉络膜中进行了 RNA 测序，并进行了组织化学分析。在体外培养的类器官中，细胞类型以类似于体内人类视网膜发育的速度成熟为稳定的“发育”状态。类器官细胞类型的转录组与成人外周视网膜细胞类型的转录组趋同。与疾病相关的基因在成人视网膜中的表达具有细胞类型特异性，并且在类器官中保留了细胞类型特异性。我们发现了一些在黄斑变性等疾病中意想不到的细胞类型。这个资源确定了在类器官中研究疾病机制和针对人类视网膜进行靶向修复的细胞靶标。
