Allen Institute for Brain Science, Seattle, WA 98109, USA.
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Science. 2017 Oct 6;358(6359):64-69. doi: 10.1126/science.aan6827.
The stereotyped spatial architecture of the brain is both beautiful and fundamentally related to its function, extending from gross morphology to individual neuron types, where soma position, dendritic architecture, and axonal projections determine their roles in functional circuitry. Our understanding of the cell types that make up the brain is rapidly accelerating, driven in particular by recent advances in single-cell transcriptomics. However, understanding brain function, development, and disease will require linking molecular cell types to morphological, physiological, and behavioral correlates. Emerging spatially resolved transcriptomic methods promise to fill this gap by localizing molecularly defined cell types in tissues, with simultaneous detection of morphology, activity, or connectivity. Here, we review the requirements for spatial transcriptomic methods toward these goals, consider the challenges ahead, and describe promising applications.
大脑刻板的空间结构既美观又与其功能有根本联系，从大体形态延伸到单个神经元类型，其中体部位置、树突结构和轴突投射决定了它们在功能回路中的作用。我们对构成大脑的细胞类型的理解正在迅速加速，特别是受到单细胞转录组学最近进展的推动。然而，要理解大脑的功能、发育和疾病，就需要将分子细胞类型与形态、生理和行为相关性联系起来。新兴的空间转录组学方法有望通过在组织中定位分子定义的细胞类型，并同时检测形态、活性或连接性来填补这一空白。在这里，我们回顾了实现这些目标的空间转录组学方法的要求，考虑了未来的挑战，并描述了有前途的应用。
