Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
Nat Commun. 2024 Sep 5;15(1):7010. doi: 10.1038/s41467-024-51186-z.
Kidney injury disrupts the intricate renal architecture and triggers limited regeneration, together with injury-invoked inflammation and fibrosis. Deciphering the molecular pathways and cellular interactions driving these processes is challenging due to the complex tissue structure. Here, we apply single cell spatial transcriptomics to examine ischemia-reperfusion injury in the mouse kidney. Spatial transcriptomics reveals injury-specific and spatially-dependent gene expression patterns in distinct cellular microenvironments within the kidney and predicts Clcf1-Crfl1 in a molecular interplay between persistently injured proximal tubule cells and their neighboring fibroblasts. Immune cell types play a critical role in organ repair. Spatial analysis identifies cellular microenvironments resembling early tertiary lymphoid structures and associated molecular pathways. Collectively, this study supports a focus on molecular interactions in cellular microenvironments to enhance understanding of injury, repair and disease.
肾脏损伤破坏了复杂的肾组织结构，并触发了有限的再生，同时伴随着损伤引发的炎症和纤维化。由于组织结构复杂，解析驱动这些过程的分子途径和细胞相互作用具有挑战性。在这里，我们应用单细胞空间转录组学来研究小鼠肾脏的缺血再灌注损伤。空间转录组学揭示了肾脏内不同细胞微环境中损伤特异性和空间依赖性的基因表达模式，并预测了在持续受损的近端肾小管细胞与其相邻成纤维细胞之间的分子相互作用中的 Clcf1-Crfl1。免疫细胞类型在器官修复中起着关键作用。空间分析确定了类似于早期三级淋巴结构的细胞微环境及其相关分子途径。总的来说，这项研究支持关注细胞微环境中的分子相互作用，以增强对损伤、修复和疾病的理解。
