Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.
Curr Opin Nephrol Hypertens. 2024 Jul 1;33(4):420-426. doi: 10.1097/MNH.0000000000000988. Epub 2024 Apr 8.
Kidney fibrosis is a key pathological aspect and outcome of chronic kidney disease (CKD). The advent of multiomic analyses using human kidney tissue, enabled by technological advances, marks a new chapter of discovery in fibrosis research of the kidney. This review highlights the rapid advancements of single-cell and spatial multiomic techniques that offer new avenues for exploring research questions related to human kidney fibrosis development.
We recently focused on understanding the origin and transition of myofibroblasts in kidney fibrosis using single-cell RNA sequencing (scRNA-seq) [1] . We analysed cells from healthy human kidneys and compared them to patient samples with CKD. We identified PDGFRα+/PDGFRβ+ mesenchymal cells as the primary cellular source of extracellular matrix (ECM) in human kidney fibrosis. We found several commonly shared cell states of fibroblasts and myofibroblasts and provided insights into molecular regulators. Novel single-cell and spatial multiomics tools are now available to shed light on cell lineages, the plasticity of kidney cells and cell-cell communication in fibrosis.
As further single-cell and spatial multiomic approaches are being developed, opportunities to apply these methods to human kidney tissues expand similarly. Careful design and optimisation of the multiomic experiments are needed to answer questions related to cell lineages, plasticity and cell-cell communication in kidney fibrosis.
目的综述：肾脏纤维化是慢性肾脏病（CKD）的一个关键病理方面和结局。技术进步使得使用人类肾脏组织进行多组学分析成为可能，标志着肾脏纤维化研究的一个新发现阶段。这篇综述强调了单细胞和空间多组学技术的快速发展，为探索与人类肾脏纤维化发展相关的研究问题提供了新的途径。
最新发现：我们最近专注于使用单细胞 RNA 测序（scRNA-seq）[1] 来理解肾脏纤维化中肌成纤维细胞的起源和转化。我们分析了健康人类肾脏的细胞，并将其与 CKD 患者的样本进行了比较。我们确定 PDGFRα+/PDGFRβ+间充质细胞是人类肾脏纤维化中细胞外基质（ECM）的主要细胞来源。我们发现了成纤维细胞和肌成纤维细胞的几个常见共同细胞状态，并提供了对分子调节剂的深入了解。新的单细胞和空间多组学工具现在可用于阐明细胞谱系、肾脏细胞的可塑性以及纤维化中的细胞间通讯。
总结：随着进一步的单细胞和空间多组学方法的发展，应用这些方法于人类肾脏组织的机会也在增加。需要仔细设计和优化多组学实验，以回答与肾脏纤维化中的细胞谱系、可塑性和细胞间通讯相关的问题。
