作者团队

Monika Piwecka, Nikolaus Rajewsky, Agnieszka Rybak-Wolf 

研究方向

单细胞和空间转录组；脑疾病

论文题目 

Single-cell and spatial transcriptomics: deciphering brain complexity in health and disease

论文摘要

In the past decade, single-cell technologies have proliferated and improved from their technically challenging beginnings to become common laboratory methods capable of determining the expression of thousands of genes in thousands of cells simultaneously. The field has progressed by taking the CNS as a primary research subject - the cellular complexity and multiplicity of neuronal cell types provide fertile ground for the increasing power of single-cell methods. Current single-cell RNA sequencing methods can quantify gene expression with sufficient accuracy to finely resolve even subtle differences between cell types and states, thus providing a great tool for studying the molecular and cellular repertoire of the CNS and its disorders. However, single-cell RNA sequencing requires the dissociation of tissue samples, which means that the interrelationships between cells are lost. Spatial transcriptomic methods bypass tissue dissociation and retain this spatial information, thereby allowing gene expression to be assessed across thousands of cells within the context of tissue structural organization. Here, we discuss how single-cell and spatially resolved transcriptomics have been contributing to unravelling the pathomechanisms underlying brain disorders. We focus on three areas where we feel these new technologies have provided particularly useful insights: selective neuronal vulnerability, neuroimmune dysfunction and cell-type-specific treatment response. We also discuss the limitations and future directions of single-cell and spatial RNA sequencing technologies.

    在过去的十年中，单细胞技术从其具有技术挑战性的开始发展并不断改进，成为能够同时测定数千个细胞中数千个基因的表达的常见实验室方法。该领域以中枢神经系统为主要研究对象，细胞的复杂性和神经元细胞类型的多样性为单细胞方法的日益强大提供了肥沃的土壤。目前的单细胞RNA测序方法可以足够准确地定量基因表达，从而精细地分辨细胞类型和状态之间的细微差异，从而为研究中枢神经系统及其疾病的分子和细胞库提供了一个很好的工具。然而，单细胞RNA测序需要将组织样本分离，这意味着丢失细胞之间的相互关系。空间转录组学方法绕过了组织解离并保留了空间信息，因此可以在组织层面的背景下评估数千个细胞的基因表达。在此，研究人员讨论了单细胞和空间解析转录组学如何有助于揭示潜在的脑疾病的病理机制。重点关注三个领域，研究人员认为这些新技术提供了特别有用的见解：选择性神经元易损性，神经免疫功能障碍和细胞类型特异性治疗反应。文中还讨论了单细胞和空间RNA测序技术的局限性和未来发展方向。