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单细胞基因组学绘制人类肾脏图谱。

Mapping the human kidney using single-cell genomics.

机构信息

Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.

Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.

出版信息

Nat Rev Nephrol. 2022 Jun;18(6):347-360. doi: 10.1038/s41581-022-00553-4. Epub 2022 Mar 17.

DOI:10.1038/s41581-022-00553-4
PMID:35301441
Abstract

The field of single-cell genomics and spatial technologies is rapidly evolving and has already provided unprecedented insights into complex tissues. Major advances have been made in dissecting the cellular composition and spatiotemporal interactions that mediate developmental processes in the fetal kidney. Single-cell technologies have also provided detailed insights into the heterogeneity of cell types within the healthy adult and shed light on the complex cellular mechanisms that contribute to kidney disease. The in-depth characterization of specific cell types associated with acute kidney injury and glomerular diseases has potential for the development of prognostic biomarkers and new therapeutics. Analyses of pathway activity in clear-cell renal cell carcinoma can predict the sensitivity of tumour cells to specific inhibitors. The identification of the cell of origin of renal cell carcinoma and of new cell types within the tumour microenvironment also has implications for the development of targeted therapeutics. Similarly, single-cell sequencing has provided new insights into the mechanisms underlying kidney fibrosis, specifically our understanding of myofibroblast origins and the contribution of cell crosstalk within the fibrotic niche to disease progression. These and future studies will enable the creation of a map to aid our understanding of the cellular processes and interactions in the developing, healthy and diseased kidney.

摘要

单细胞基因组学和空间技术领域正在迅速发展,已经为复杂组织提供了前所未有的见解。在解析介导胎儿肾脏发育过程的细胞组成和时空相互作用方面取得了重大进展。单细胞技术还深入了解了健康成年人体内细胞类型的异质性,并揭示了导致肾脏疾病的复杂细胞机制。与急性肾损伤和肾小球疾病相关的特定细胞类型的深入特征分析有可能开发出预后生物标志物和新的治疗方法。透明细胞肾细胞癌中途径活性的分析可以预测肿瘤细胞对特定抑制剂的敏感性。肾细胞癌的起源细胞和肿瘤微环境内新的细胞类型的鉴定也对靶向治疗的发展具有重要意义。同样,单细胞测序为肾脏纤维化的机制提供了新的见解,特别是我们对肌成纤维细胞起源的理解以及纤维化龛内细胞串扰对疾病进展的贡献。这些和未来的研究将使我们能够创建一个图谱,以帮助我们理解发育、健康和患病肾脏中的细胞过程和相互作用。

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人类肾脏疾病的多组学分析确定了一种可治疗的炎症性和促纤维化肾小管细胞表型。
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Heterogeneous and novel transcript expression in single cells of patient-derived clear cell renal cell carcinoma organoids.患者来源的透明细胞肾细胞癌类器官单细胞中的异质性和新型转录本表达
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PPDPF preserves integrity of proximal tubule by modulating NMNAT activity in chronic kidney diseases.PPDPF通过调节慢性肾脏病中烟酰胺单核苷酸腺苷转移酶(NMNAT)的活性来维持近端肾小管的完整性。
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