单细胞测序技术在肝脏疾病的应用与展望

新兴的单细胞测序技术能够从单细胞水平揭示基因组、转录组和表观遗传学等分子水平发生的基因变异与表观修饰状态,也可用于鉴定新的细胞类型和表面标记物。这将帮助人们探明疾病发生时细胞基因、转录或表观修饰方面的变化,了解细胞之间的联系,以及深入理解肿瘤异质性。目前,单细胞测序技术已用于多种疾病的研究,其在肝脏疾病,包括肝硬化、肝癌中已有相关成果。于此,综述了单细胞测序技术在肝脏发育及肝病中的应用,讨论了肝脏疾病发生的内在机制以及该技术仍存在的问题,提出可能的解决方案,如发展三维单细胞测序技术将更能帮助人们深刻理解肝脏疾病发生机制。     

Single-cell analysis of tumors: Creating new value for molecular biomarker discovery of cancer stem cells and tumor-infiltrating immune cells

Biomarker-driven individualized treatment in oncology has made tremendous progress through technological developments, new therapeutic modalities and a deeper understanding of the molecular biology for tumors, cancer stem cells and tumor-infiltrating immune cells. Recent technical developments have led to the establishment of a variety of cancer-related diagnostic, prognostic and predictive biomarkers. In this regard, different modern OMICs approaches were assessed in order to categorize and classify prognostically different forms of neoplasia. Despite those technical advancements, the extent of molecular heterogeneity at the individual cell level in human tumors remains largely uncharacterized. Each tumor consists of a mixture of heterogeneous cell types. Therefore, it is important to quantify the dynamic cellular variations in order to predict clinical parameters, such as a response to treatment and or potential for disease recurrence. Recently, single-cell based methods have been developed to characterize the heterogeneity in seemingly homogenous cancer cell populations prior to and during treatment. In this review, we highlight the recent advances for single-cell analysis and discuss the challenges and prospects for molecular characterization of cancer cells, cancer stem cells and tumor-infiltrating immune cells.     

空间转录物组学技术进展及其在神经科学领域中的应用

空间转录物组学是在单细胞RNA测序技术基础上实现细胞空间位置信息测定的组学技术。该技术克服了单细胞转录物组学在单细胞分离建库过程中丢失细胞在组织中空间信息的问题,可同时提供研究对象的转录物组数据信息和在组织中的空间位置信息。空间转录物组学技术对研究细胞谱系的发生过程、细胞间的调控机制和相互作用等具有重要作用,是组学技术研究的重要发展方向和热点。近年来,空间转录物组学技术发展迅速,新的检测方法不断产生,检测灵敏度、分辨率和检测通量等技术指标不断提升。本文根据获取空间信息的原理不同,将较为常用的空间转录物组学技术进行了分类,总结了各类方法的检测原理、代表性技术手段及其相应的技术指标。随后,从脑细胞类型区分与细胞层图谱构建、神经系统相关疾病特征分析与标志物研究两个方面举例论述了空间转录物组学技术在神经科学中的应用。最后,对空间转录物组学技术目前存在的问题进行了总结,并对其未来的发展方向进行了展望。     

Application of single-cell technology in cancer research

In this review, we have outlined the application of single-cell technology in cancer research. Single-cell technology has made encouraging progress in recent years and now provides the means to detect rare cancer cells such as circulating tumor cells and cancer stem cells. We reveal how this technology has advanced the analysis of intratumor heterogeneity and tumor epigenetics, and guided individualized treatment strategies. The future prospects now are to bring single-cell technology into the clinical arena. We believe that the clinical application of single-cell technology will be beneficial in cancer diagnostics and treatment, and ultimately improve survival in cancer patients.