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肾脏精准医学项目与近端小管损伤的单细胞生物学

The Kidney Precision Medicine Project and Single-Cell Biology of the Injured Proximal Tubule.

作者信息

Janosevic Danielle, De Luca Thomas, Eadon Michael T

机构信息

Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana.

Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana.

出版信息

Am J Pathol. 2025 Jan;195(1):7-22. doi: 10.1016/j.ajpath.2024.09.006. Epub 2024 Sep 26.

Abstract

Single-cell RNA sequencing (scRNA-seq) has led to major advances in our understanding of proximal tubule subtypes in health and disease. The proximal tubule serves essential functions in overall homeostasis, but pathologic or physiological perturbations can affect its transcriptomic signature and corresponding tasks. These alterations in proximal tubular cells are often described within a scRNA-seq atlas as cell states, which are pathophysiological subclassifications based on molecular and morphologic changes in a cell's response to that injury compared with its native state. This review describes the major cell states defined in the Kidney Precision Medicine Project's scRNA-seq atlas. It then identifies the overlap between the Kidney Precision Medicine Project and other seminal works that may use different nomenclature or cluster proximal tubule cells at different resolutions to define cell state subtypes. The goal is for the reader to understand the key transcriptomic markers of important cellular injury and regeneration processes across this highly dynamic and evolving field.

摘要

单细胞RNA测序(scRNA-seq)在我们对健康和疾病状态下近端肾小管亚型的理解方面取得了重大进展。近端肾小管在整体内环境稳态中发挥着重要功能,但病理或生理扰动会影响其转录组特征及相应功能。在scRNA-seq图谱中,近端肾小管细胞的这些改变通常被描述为细胞状态,即基于细胞对损伤反应时与正常状态相比分子和形态变化的病理生理亚分类。本综述描述了肾脏精准医学项目scRNA-seq图谱中定义的主要细胞状态。然后确定了肾脏精准医学项目与其他开创性研究之间的重叠部分,这些研究可能使用不同的命名法或在不同分辨率下对近端肾小管细胞进行聚类以定义细胞状态亚型。目的是让读者了解这个高度动态且不断发展的领域中重要细胞损伤和再生过程的关键转录组标记。

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