Improved understanding of the cellular changes and interactions that occur in the kidney following injury may help to elucidate the mechanisms that govern the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) and aid the development of therapeutic interventions. In new research, Michal Polonsky, Louisa Gerhardt and colleagues use single-cell spatial transcriptomics to uncover injury-specific and spatially dependent gene expression patterns in distinct cellular microenvironments within the mouse kidney following ischaemia–reperfusion injury.

Using sequential fluorescence in situ hybridization (seqFISH), the researchers identified 17 microenvironments, comprising neighbourhoods of distinct cell type compositions within the kidney. Nine of the microenvironments differed between healthy control and injured samples. One of these, ME-5, contained the highest density of injured proximal tubule cells, as well as fibroblasts and immune cells, in the AKI samples. Analyses of ligand–receptor interactions within ME-5 identified an upregulation of CLCF1–CRLF1 signalling between persistently injured proximal tubule cells and their neighbouring fibroblasts. Another microenvironment, ME-16, resembled a tertiary lymphoid structure, containing CD4⁺ T cells and T regulatory cells, as well as pro-inflammatory macrophages.

更好地了解损伤后肾脏中发生的细胞变化和相互作用可能有助于阐明控制从急性肾损伤 （AKI） 转变为慢性肾病 （CKD） 的机制，并有助于开发治疗干预措施。在新的研究中，Michal Polonsky、Louisa Gerhardt 及其同事使用单细胞空间转录组学来揭示缺血再灌注损伤后小鼠肾脏内不同细胞微环境中的损伤特异性和空间依赖性基因表达模式。

使用顺序荧光原位杂交 （seqFISH），研究人员确定了 17 个微环境，包括肾脏内不同细胞类型组成的邻域。其中 9 个微环境在健康对照和受伤样本之间存在差异。其中一种 ME-5 在 AKI 样本中含有密度最高的受伤近端小管细胞以及成纤维细胞和免疫细胞。对 ME-5 内配体-受体相互作用的分析确定了持续受伤的近端小管细胞与其邻近成纤维细胞之间 CLCF1-CRLF1 信号的上调。另一个微环境 ME-16 类似于三级淋巴结构，包含 CD4⁺ T 细胞和 T 调节细胞，以及促炎巨噬细胞。