Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury.
Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury.
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DOI：
10.1186/s13073-022-01108-9
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发表时间：
2022-09-09
期刊：
影响因子：
12.3
通讯作者：
中科院分区：
文献类型：
--
作者：
急性肾损伤（阿基）经常发生在重症患者中，并与不良结局相关。阿基和肾细胞对损伤反应的细胞机制仍不完全清楚。我们对8名重度阿基患者（根据肾脏疾病：改善全球结局（KDIGO）标准为2期或3期）的肾组织进行了单核转录组学、批量转录组学、分子成像研究和常规组织学检查。样本是在个体死于与呼吸道感染相关的危重疾病后1-2小时内获得的，8名个体中有4名被诊断为COVID-19。对照肾组织是在死后或肾切除术后从没有阿基的个体获得的。受阿基影响的人肾脏的高深度单细胞分辨基因表达数据显示，肾小管上皮细胞的主要细胞类型中，特别是近端小管、粗升支和远曲小管中，新的损伤相关细胞状态富集。四个不同的，层次上相互关联的损伤细胞状态是可区分的，其特征在于转录组模式与氧化应激，缺氧，干扰素反应，上皮细胞间质转化，分别。阿基患者之间的转录组差异主要由这四种损伤亚型的细胞类型特异性丰度驱动，而不是由私人分子反应驱动。患有和没有COVID-19的个体之间AKI相关的基因表达变化相似。该研究提供了与人类重症相关阿基相关的细胞类型特异性转录组学反应的广泛资源，突出了复发性疾病相关特征和个体间异质性。人类阿基的个性化分子疾病评估可能会促进定制疗法的开发。 在线版本包含补充材料，可通过10.1186/s13073-022-01108-9获得。
Acute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood. We performed single-nuclei transcriptomics, bulk transcriptomics, molecular imaging studies, and conventional histology on kidney tissues from 8 individuals with severe AKI (stage 2 or 3 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria). Specimens were obtained within 1–2 h after individuals had succumbed to critical illness associated with respiratory infections, with 4 of 8 individuals diagnosed with COVID-19. Control kidney tissues were obtained post-mortem or after nephrectomy from individuals without AKI. High-depth single cell-resolved gene expression data of human kidneys affected by AKI revealed enrichment of novel injury-associated cell states within the major cell types of the tubular epithelium, in particular in proximal tubules, thick ascending limbs, and distal convoluted tubules. Four distinct, hierarchically interconnected injured cell states were distinguishable and characterized by transcriptome patterns associated with oxidative stress, hypoxia, interferon response, and epithelial-to-mesenchymal transition, respectively. Transcriptome differences between individuals with AKI were driven primarily by the cell type-specific abundance of these four injury subtypes rather than by private molecular responses. AKI-associated changes in gene expression between individuals with and without COVID-19 were similar. The study provides an extensive resource of the cell type-specific transcriptomic responses associated with critical illness-associated AKI in humans, highlighting recurrent disease-associated signatures and inter-individual heterogeneity. Personalized molecular disease assessment in human AKI may foster the development of tailored therapies. The online version contains supplementary material available at 10.1186/s13073-022-01108-9.
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影响因子：
6
作者：
Hardenberg JB;Stockmann H;Aigner A;Gotthardt I;Enghard P;Hinze C;Balzer F;Schmidt D;Zickler D;Kruse J;Körner R;Stegemann M;Schneider T;Schumann M;Müller-Redetzky H;Angermair S;Budde K;Weber-Carstens S;Witzenrath M;Treskatsch S;Siegmund B;Spies C;Suttorp N;Rauch G;Eckardt KU;Schmidt-Ott KM
通讯作者：
Schmidt-Ott KM
临床综述：氧作为信号分子。
DOI：
10.1186/cc9185
发表时间：
2010
期刊：
Critical care (London, England)
影响因子：
--
作者：
Bartz RR;Piantadosi CA
通讯作者：
Piantadosi CA
影响因子：
14.9
作者：
Gillespie M;Jassal B;Stephan R;Milacic M;Rothfels K;Senff-Ribeiro A;Griss J;Sevilla C;Matthews L;Gong C;Deng C;Varusai T;Ragueneau E;Haider Y;May B;Shamovsky V;Weiser J;Brunson T;Sanati N;Beckman L;Shao X;Fabregat A;Sidiropoulos K;Murillo J;Viteri G;Cook J;Shorser S;Bader G;Demir E;Sander C;Haw R;Wu G;Stein L;Hermjakob H;D'Eustachio P
通讯作者：
D'Eustachio P
DOI：
10.1097/01.asn.0000067652.51441.21
发表时间：
2003-06-01
影响因子：
13.6
作者：
Bonventre, JV
通讯作者：
Bonventre, JV
影响因子：
15.1
作者：
Bhatraju, Pavan K.;Mukherjee, Paramita;Wurfel, Mark M.
通讯作者：
Wurfel, Mark M.