Department of Medicine, University of Cambridge, Cambridge, UK.
Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK.
J Pathol. 2020 Apr;250(5):693-704. doi: 10.1002/path.5417. Epub 2020 Mar 31.
Cells represent the basic building blocks of living organisms. Accurate characterisation of cellular phenotype, intercellular signalling networks, and the spatial organisation of cells within organs is crucial to deliver a better understanding of the processes underpinning physiology, and the perturbations that lead to disease. Single-cell methodologies have increased rapidly in scale and scope in recent years and are set to generate important insights into human disease. Here, we review current practices in nephropathology, which are dominated by relatively simple morphological descriptions of tissue biopsies based on their appearance using light microscopy. Bulk transcriptomics have more recently been used to explore glomerular and tubulointerstitial kidney disease, renal cancer, and the responses to injury and alloimmunity in kidney transplantation, generating novel disease insights and prognostic biomarkers. These studies set the stage for single-cell transcriptomic approaches that reveal cell-type-specific gene expression patterns in health and disease. These technologies allow genome-wide disease susceptibility genes to be interpreted with the knowledge of the specific cell populations within organs that express them, identifying candidate cell types for further study. Single-cell technologies are also moving beyond assaying individual cellular transcriptomes, to measuring the epigenetic landscape of single cells. Single-cell antigen-receptor gene sequencing also enables specific T- and B-cell clones to be tracked in different tissues and disease states. In the coming years these rich 'multi-omic' descriptions of kidney disease will enable histopathological descriptions to be comprehensively integrated with molecular phenotypes, enabling better disease classification and prognostication and the application of personalised treatment strategies. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
细胞是构成生物体的基本单位。准确描述细胞表型、细胞间信号网络以及细胞在器官内的空间组织，对于深入了解生理过程以及导致疾病的干扰因素至关重要。近年来，单细胞方法在规模和范围上都有了迅速的发展，并有望为人类疾病提供重要的见解。在这里，我们回顾了肾病学的当前实践，肾病学主要基于光镜下组织活检的相对简单的形态描述。批量转录组学最近也被用于探索肾小球和肾小管间质肾脏疾病、肾细胞癌以及肾移植中的损伤和同种异体免疫反应，产生了新的疾病见解和预后生物标志物。这些研究为揭示健康和疾病中特定细胞类型的基因表达模式的单细胞转录组学方法奠定了基础。这些技术使全基因组疾病易感性基因的解读能够与器官内表达这些基因的特定细胞群体的知识相结合，确定进一步研究的候选细胞类型。单细胞技术也不仅仅局限于检测单个细胞的转录组，还可以测量单个细胞的表观遗传景观。单细胞抗原受体基因测序还可以在不同的组织和疾病状态下跟踪特定的 T 细胞和 B 细胞克隆。在未来几年，这些丰富的“多组学”肾脏疾病描述将使组织病理学描述能够与分子表型全面整合，从而更好地进行疾病分类和预后预测，并应用个性化治疗策略。
