Department of Chemistry and the Beckman Institute, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
ACS Chem Neurosci. 2018 Jan 17;9(1):40-50. doi: 10.1021/acschemneuro.7b00304. Epub 2017 Oct 19.
Metabolomics, the characterization of metabolites and their changes within biological systems, has seen great technological and methodological progress over the past decade. Most metabolomic experiments involve the characterization of the small-molecule content of fluids or tissue homogenates. While these microliter and larger volume metabolomic measurements can characterize hundreds to thousands of compounds, the coverage of molecular content decreases as sample sizes are reduced to the nanoliter and even to the picoliter volume range. Recent progress has enabled the ability to characterize the major molecules found within specific individual cells. Especially within the brain, a myriad of cell types are colocalized, and oftentimes only a subset of these cells undergo changes in both healthy and pathological states. Here we highlight recent progress in mass spectrometry-based approaches used for single cell metabolomics, emphasizing their application to neuroscience research. Single cell studies can be directed to measuring differences between members of populations of similar cells (e.g., oligodendrocytes), as well as characterizing differences between cell types (e.g., neurons and astrocytes), and are especially useful for measuring changes occurring during different behavior states, exposure to diets and drugs, neuronal activity, and disease. When combined with other omics approaches such as transcriptomics, and with morphological and physiological measurements, single cell metabolomics aids fundamental neurochemical studies, has great potential in pharmaceutical development, and should improve the diagnosis and treatment of brain diseases.
代谢组学是对生物系统内代谢物及其变化的特征描述，在过去十年中取得了巨大的技术和方法学进展。大多数代谢组学实验都涉及对液体或组织匀浆中小分子含量的特征描述。虽然这些微升和更大体积的代谢组学测量可以描述数百到数千种化合物，但随着样本量减少到纳升甚至皮升体积范围，分子含量的覆盖范围会减少。最近的进展使我们能够描述特定单个细胞内发现的主要分子。特别是在大脑中，有许多细胞类型聚集在一起，而且在健康和病理状态下，通常只有这些细胞的一部分发生变化。在这里，我们重点介绍了基于质谱的单细胞代谢组学方法的最新进展，强调了它们在神经科学研究中的应用。单细胞研究可以用于测量相似细胞群体成员之间的差异（例如少突胶质细胞），以及表征细胞类型之间的差异（例如神经元和星形胶质细胞），并且特别适用于测量不同行为状态、饮食和药物暴露、神经元活动和疾病期间发生的变化。当与转录组学等其他组学方法以及形态学和生理学测量相结合时，单细胞代谢组学有助于基础神经化学研究，在药物开发方面具有巨大的潜力，并应改善大脑疾病的诊断和治疗。
