Human neural organoids, generated from pluripotent stem cells in vitro, are useful tools to study human brain development, evolution and disease. However, it is unclear which parts of the human brain are covered by existing protocols, and it has been difficult to quantitatively assess organoid variation and fidelity. Here we integrate 36 single-cell transcriptomic datasets spanning 26 protocols into one integrated human neural organoid cell atlas totalling more than 1.7 million cells^{1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26}. Mapping to developing human brain references^27,28,29,30 shows primary cell types and states that have been generated in vitro, and estimates transcriptomic similarity between primary and organoid counterparts across protocols. We provide a programmatic interface to browse the atlas and query new datasets, and showcase the power of the atlas to annotate organoid cell types and evaluate new organoid protocols. Finally, we show that the atlas can be used as a diverse control cohort to annotate and compare organoid models of neural disease, identifying genes and pathways that may underlie pathological mechanisms with the neural models. The human neural organoid cell atlas will be useful to assess organoid fidelity, characterize perturbed and diseased states and facilitate protocol development.

由体外多能干细胞产生的人类神经类器官是研究人类大脑发育、进化和疾病的有用工具。然而，目前尚不清楚现有方案涵盖了人脑的哪些部分，并且很难定量评估类器官变异和保真度。在这里，我们将跨越 26 个方案的 36 个单细胞转录组数据集整合到一个集成的人类神经类器官细胞图谱中，总计超过 170 万个细胞^{1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26}。映射到发育中的人脑参考文献^27,28,29,30 显示了在体外产生的原代细胞类型和状态，并估计了不同方案中原代细胞和类器官对应物之间的转录组相似性。我们提供了一个编程界面来浏览图谱和查询新数据集，并展示了图谱在注释类器官细胞类型和评估新类器官方案方面的强大功能。最后，我们表明该图谱可以用作多样化的对照队列来注释和比较神经疾病的类器官模型，识别可能构成神经模型病理机制基础的基因和通路。人类神经类器官细胞图谱将有助于评估类器官保真度、表征扰动和疾病状态并促进方案开发。