小柯机器人

美国圣路易斯华盛顿大学Benjamin D. Humphreys团队近期取得重要工作进展，他们通过综合单细胞转录分析确定了肾脏纤维化期间共同和独特的上皮细胞损伤反应。相关研究成果2022年10月19日在线发表于《细胞—代谢》杂志上。

研究人员采用单细胞组合索引RNA测序法分析了两种纤维化模型的24个小鼠肾脏。他们在一次实验中分析了309,666个细胞，代表了50种细胞类型/状态，包括上皮细胞、内皮细胞、免疫细胞和基质细胞群。单细胞分析确定了近端肾小管的不同损伤状态，包括两个不同的早期阶段人群，分别具有脂质和氨基酸代谢失调的特点。脂质代谢在慢性阶段是有缺陷的，但在缺血诱导损伤的早期阶段被暂时激活，脂质沉积和脂肪酸β-氧化都会增加。

Perilipin 2被确定为细胞内脂滴的表面标记，其在体外的敲除破坏了脂质积累期间的细胞能量状态维护。通过对整个肾脏部分的上皮细胞进行调查，确定了共同和独特的损伤反应。基质细胞表现出高度的异质性，并通过上皮-基质相互作用促进了纤维化的形成。

据介绍，驱动肾脏纤维化和代谢功能障碍的基本细胞事件并不完全了解。

附：英文原文

Title: Comprehensive single-cell transcriptional profiling defines shared and unique epithelial injury responses during kidney fibrosis

Author: Haikuo Li, Eryn E. Dixon, Haojia Wu, Benjamin D. Humphreys

Issue&Volume: 2022-10-19

Abstract: The underlying cellular events driving kidney fibrogenesis and metabolic dysfunctionare incompletely understood. Here, we employed single-cell combinatorial indexingRNA sequencing to analyze 24 mouse kidneys from two fibrosis models. We profiled 309,666cells in one experiment, representing 50 cell types/states encompassing epithelial,endothelial, immune, and stromal populations. Single-cell analysis identified diverseinjury states of the proximal tubule, including two distinct early-phase populationswith dysregulated lipid and amino acid metabolism, respectively. Lipid metabolismwas defective in the chronic phase but was transiently activated in the very earlystages of ischemia-induced injury, where we discovered increased lipid depositionand increased fatty acid β-oxidation. Perilipin 2 was identified as a surface markerof intracellular lipid droplets, and its knockdown in vitro disrupted cell energy state maintenance during lipid accumulation. Surveying epithelialcells across nephron segments identified shared and unique injury responses. Stromalcells exhibited high heterogeneity and contributed to fibrogenesis by epithelial-stromalcrosstalk.

DOI: 10.1016/j.cmet.2022.09.026

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00450-8

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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