Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
Max Planck Institute for Evolutionary Anthropology, Leipzig, 04103 Sachsen, Germany.
Cell Stem Cell. 2021 Jun 3;28(6):1148-1159.e8. doi: 10.1016/j.stem.2021.02.015. Epub 2021 Mar 11.
Self-organizing tissues resembling brain structures generated from human stem cells offer exciting possibilities to study human brain development, disease, and evolution. These 3D models are complex and can contain cells at various stages of differentiation from different brain regions. Single-cell genomic methods provide powerful approaches to explore cell composition, differentiation trajectories, and genetic perturbations in brain organoid systems. However, it remains a major challenge to understand the heterogeneity observed within and between individual organoids. Here, we develop a set of computational tools (VoxHunt) to assess brain organoid patterning, developmental state, and cell identity through comparisons to spatial and single-cell transcriptome reference datasets. We use VoxHunt to characterize and visualize cell compositions using single-cell and bulk genomic data from multiple organoid protocols modeling different brain structures. VoxHunt will be useful to assess organoid engineering protocols and to annotate cell fates that emerge in organoids during genetic and environmental perturbation experiments.
自组织的组织类似于由人类干细胞生成的脑结构，为研究人类大脑发育、疾病和进化提供了令人兴奋的可能性。这些 3D 模型非常复杂，可包含来自不同脑区的处于不同分化阶段的细胞。单细胞基因组学方法为探索脑类器官系统中的细胞组成、分化轨迹和遗传干扰提供了强大的方法。然而，理解单个类器官内和之间观察到的异质性仍然是一个主要挑战。在这里，我们开发了一组计算工具（VoxHunt），通过与空间和单细胞转录组参考数据集的比较，评估脑类器官的模式形成、发育状态和细胞身份。我们使用 VoxHunt 来使用来自不同脑结构建模的多个类器官方案的单细胞和批量基因组数据来描述和可视化细胞组成。VoxHunt 将有助于评估类器官工程方案，并注释在遗传和环境干扰实验中类器官中出现的细胞命运。
