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

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

Heteroepitaxial B12As2 on silicon substrates

The morphology and crystal structure of rhombohedral B[subscript 12]As[subscript 2] thin films prepared by chemical vapor deposition on Si (100), Si (110) and Si (111) substrates were examined. For short depositions, 30 seconds at 1300 °C, the B[subscript 12]As[subscript 2] nucleated in patterns that were unique to each substrate orientation, probably due to variations in the surface atomic structure and surface activation energy of the substrates. Small square domains, one dimensional straight lines, and irregular lines were the representative morphologies on Si (100), Si (111) and Si (110), respectively. For long deposition, 30 minutes at 1300 °C, continuous thin films of B[subscript 12]As[subscript 2] formed with distinct morphologies also dependent on the orientation of the substrates. “Cross”, “wire” and “chain” morphologies were formed on the Si (100), Si (111) and Si (110) substrates, respectively. X-ray diffraction showed that the B[subscript 12]As[subscript 2] films had the following predominant oriented textures: B[subscript 12]As[subscript 2] (110) on Si(100), B[subscript 12]As[subscript 2] (101) on Si(111), and B[subscript 12]As[subscript 2] (001) on Si(110). The in-plane orientations of the B[subscript 12]As[subscript 2] films as determined by XRD pole figures, is also reported