دورية أكاديمية
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Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury

التفاصيل البيبلوغرافية
العنوان: Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury
المؤلفون: Christian Hinze, Christine Kocks, Janna Leiz, Nikos Karaiskos, Anastasiya Boltengagen, Shuang Cao, Christopher Mark Skopnik, Jan Klocke, Jan-Hendrik Hardenberg, Helena Stockmann, Inka Gotthardt, Benedikt Obermayer, Laleh Haghverdi, Emanuel Wyler, Markus Landthaler, Sebastian Bachmann, Andreas C. Hocke, Victor Corman, Jonas Busch, Wolfgang Schneider, Nina Himmerkus, Markus Bleich, Kai-Uwe Eckardt, Philipp Enghard, Nikolaus Rajewsky, Kai M. Schmidt-Ott
المصدر: Genome Medicine, Vol 14, Iss 1, Pp 1-18 (2022)
بيانات النشر: BMC, 2022.
سنة النشر: 2022
المجموعة: LCC:Medicine
LCC:Genetics
مصطلحات موضوعية: Acute kidney injury, Critical illness, Single-cell sequencing, Medicine, Genetics, QH426-470
الوصف: Abstract Background 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. Methods 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. Results 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. Conclusions 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1756-994X
Relation: https://doaj.org/toc/1756-994X
DOI: 10.1186/s13073-022-01108-9
URL الوصول: https://doaj.org/article/2152453158884a80961272912072ce81
رقم الأكسشن: edsdoj.2152453158884a80961272912072ce81
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1756994X
DOI:10.1186/s13073-022-01108-9