Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats

作者：Zhu Wang, Qiong Deng, Yanli Gu, Min Li, Yeda Chen, Jieyan Wang, Ying Zhang, Jianwen Zhang, Qiyi Hu, Shenping Zhang, Wei Chen, Zhenhua Chen, Jiaying Li, Xi‐Sheng Wang, Hui Liang · 发表于：Cell & Bioscience · 年份：2023 · DOI：10.1186/s13578-023-01041-3 · 被引用次数：14 · 研究领域：Kidney Stones and Urolithiasis Treatments、Acute Kidney Injury Research、Pancreatitis Pathology and Treatment

Abstract Background Urolithiasis with high prevalence and recurrence rate, has impacts on kidney injury in patients, becomes a socioeconomic and healthcare problem in worldwide. However, the biology of kidney with crystal formation and proximal tubular injury remains essentially unclear. The present study aims to evaluate the cell biology and immune-communications in urolithiasis mediated kidney injury, to provide new insights in the kidney stone treatment and prevention. Results We identified 3 distinct injured-proximal tubular cell types based on the differentially expression injury markers (Havcr1 and lcn2) and functional solute carriers (slc34a3, slc22a8, slc38a3 and slc7a13), and characterized 4 main immune cell types in kidney and one undefined cell population, where F13a1 +/high /CD163 +/high monocyte & macrophage and Sirpa/Fcgr1a/Fcgr2a +/high granulocyte were the most enriched. We performed intercellular crosstalk analysis based on the snRNA-seq data and explored the potential immunomodulation of calculi stone formation, and founded that the interaction between ligand Gas6 and its receptors (Gas6-Axl, Gas6-Mertk) was specifically observed in the injured-PT1 cells, but not injured-PT2 and -PT3 cells. The interaction of Ptn-Plxnb2 was only observed between the injured-PT3 cells and its receptor enriched cells. Conclusions Present study comprehensively characterized the gene expression profile in the calculi rat kidney at single nucleus level, identified novel marke...