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Single-nucleus atlas of the human kidney papilla identifies significant immune injury in patients with stone disease

ABSTRACT: Single-nucleus atlas of the human kidney papilla identifies significant immune injury in patients with stone disease

PROVIDER: PRJNA966977 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24420668_1.fastq.gz	Fastqsanger.gz
	SRR24420668_2.fastq.gz	Fastqsanger.gz
	SRR24420669_1.fastq.gz	Fastqsanger.gz
	SRR24420669_2.fastq.gz	Fastqsanger.gz
	SRR24420670_1.fastq.gz	Fastqsanger.gz

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Single-nucleus atlas of the human kidney papilla identifies significant immune injury in patients with stone disease

Project description:Kidney stone disease causes significant morbidity and increases health care utilization. In this dataset, we applied a single-nucleus assay to renal papila samples in order to charachterize the cellular and molecular niches in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.

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A Spatial Transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease

Project description:Kidney stone disease causes significant morbidity and increases health care utilization. The pathogenesis of stone disease is incompletely understood, due in part to the poor characterization of the cellular and molecular makeup of the human papilla and its alteration with disease. In this work, we characterize the human renal papilla in health and calcium oxalate stone disease using single nuclear RNA sequencing, spatial transcriptomics and high-resolution large scale multiplexed 3D and Co-Detection by indexing (CODEX) imaging. We define and localize subtypes of principal cells enriched in the papilla as well as immune and stromal cell populations. We further uncovered an undifferentiated epithelial cell signature in the papilla, particularly during nephrolithiasis.

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Project description:Comparison between renal papilla tissue with and without the presence of calcified Randall’s plaques, and between the papilla, medulla, and cortex regions from within a single recurrent stone forming kidney demonstrated that patterns of gene expression between the papilla, medulla, and cortex that distinguished these three regions from one another. Disease and function analysis of these gene sets demonstrated up-regulation of genes related to urinary/renal disorders, granulocyte response, vascular smooth muscle cell proliferation, dehydration, and renal calcification and down-regulation of genes related to carboxylic acid/ lipid/ fatty acid transport and urine osmolality.

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