Comprehensive single-cell transcriptional profiling defines shared and unique epithelial injury responses during kidney fibrosis.
Comprehensive single-cell transcriptional profiling defines shared and unique epithelial injury responses during kidney fibrosis.
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DOI：
10.1016/j.cmet.2022.09.026
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发表时间：
2022-12-06
期刊：
影响因子：
29
通讯作者：
Humphreys, Benjamin D.
中科院分区：
文献类型：
--
作者：
Li, Haikuo;Dixon, Eryn E.;Wu, Haojia;Humphreys, Benjamin D.
驱动肾脏纤维形成和代谢功能障碍的潜在细胞事件尚不完全清楚。在这里，我们采用单细胞组合索引 RNA 测序来分析来自两个纤维化模型的 24 个小鼠肾脏。我们在一项实验中分析了 309,666 个细胞，代表 50 种细胞类型/状态，涵盖上皮细胞、内皮细胞、免疫细胞和基质细胞群。单细胞分析确定了近曲小管的不同损伤状态，包括两个分别具有脂质和氨基酸代谢失调的不同早期群体。脂质代谢在慢性期存在缺陷，但在缺血引起的损伤的早期阶段短暂激活，我们发现脂质沉积增加和脂肪酸β-氧化增加。 Perilipin 2 被确定为细胞内脂滴的表面标记物，其体外敲除破坏了脂质积累过程中细胞能量状态的维持。对肾单位段上皮细胞的调查发现了共同和独特的损伤反应。基质细胞表现出高度异质性，并通过上皮基质串扰促进纤维形成。李等人。使用单细胞组合索引 RNA 测序分析小鼠肾纤维化的全时过程。他们描述了近端肾小管细胞的多种损伤状态，包括在缺血引起的损伤的早期阶段脂质代谢增强的一种细胞状态。该单细胞图谱定义了纤维化过程中的肾上皮损伤反应。
The underlying cellular events driving kidney fibrogenesis and metabolic dysfunction are incompletely understood. Here, we employed single-cell combinatorial indexing RNA-sequencing to analyze 24 mouse kidneys from two fibrosis models. We profiled 309,666 cells in one experiment, representing 50 cell types/states encompassing epithelial, endothelial, immune and stromal populations. Single-cell analysis identified diverse injury states of the proximal tubule, including two distinct early-phase populations with dysregulated lipid and amino acid metabolism, respectively. Lipid metabolism was defective in the chronic phase but was transiently activated in the very early stages of ischemia-induced injury, where we discovered increased lipid deposition and increased fatty acid β-oxidation. Perilipin 2 was identified as a surface marker of intracellular lipid droplets and its knockdown in vitro disrupted cell energy state maintenance during lipid accumulation. Surveying epithelial cells across nephron segments identified shared and unique injury responses. Stromal cells exhibited high heterogeneity and contributed to fibrogenesis by epithelial-stromal crosstalk. Li et al. profile the full-time courses of mouse kidney fibrogenesis using single-cell combinatorial indexing RNA-sequencing. They describe diverse injury states of proximal tubular cells, including one cell state with enhanced lipid metabolism at an early phase of ischemia-induced injury. This single-cell atlas defines kidney epithelial injury responses in fibrosis.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.8
作者：
Gao, J;Serrero, G
通讯作者：
Serrero, G
PLIN2 是胰腺 β 细胞中未折叠蛋白反应和内质网应激消解的关键调节因子。
影响因子：
4.6
作者：
Chen E;Tsai TH;Li L;Saha P;Chan L;Chang BH
通讯作者：
Chang BH
DOI：
10.1073/pnas.2026684118
发表时间：
2021-07-06
影响因子：
11.1
作者：
Gerhardt LMS;Liu J;Koppitch K;Cippà PE;McMahon AP
通讯作者：
McMahon AP