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A reference tissue atlas for the human kidney.

ABSTRACT: Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.

SUBMITTER: Hansen J

PROVIDER: S-EPMC9176741 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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A reference tissue atlas for the human kidney.

Hansen Jens J Sealfon Rachel R Menon Rajasree R Eadon Michael T MT Lake Blue B BB Steck Becky B Anjani Kavya K Parikh Samir S Sigdel Tara K TK Zhang Guanshi G Velickovic Dusan D Barwinska Daria D Alexandrov Theodore T Dobi Dejan D Rashmi Priyanka P Otto Edgar A EA Rivera Miguel M Rose Michael P MP Anderton Christopher R CR Shapiro John P JP Pamreddy Annapurna A Winfree Seth S Xiong Yuguang Y He Yongqun Y de Boer Ian H IH Hodgin Jeffrey B JB Barisoni Laura L Naik Abhijit S AS Sharma Kumar K Sarwal Minnie M MM Zhang Kun K Himmelfarb Jonathan J Rovin Brad B El-Achkar Tarek M TM Laszik Zoltan Z He John Cijiang JC Dagher Pierre C PC Valerius M Todd MT Jain Sanjay S Satlin Lisa M LM Troyanskaya Olga G OG Kretzler Matthias M Iyengar Ravi R Azeloglu Evren U EU

Science advances 20220608 23

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and COD ...[more]

PMID: 35675394

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Project description:BackgroundHuman-resident microbes can influence both health and disease. Investigating the microbiome using next-generation sequencing technology has revealed examples of mutualism and conflict between microbes and humans. Comparing to bacteria, the viral component of the microbiome (i.e., the "virome") is understudied. Somatic tissues of healthy individuals are usually inaccessible for the virome sampling; therefore, there is limited understanding of the presence and distribution of viruses in tissues in healthy individuals and how virus infection associates with human gene expression and perturbs immunological homeostasis.ResultsTo characterize the human virome in a tissue-specific manner, here we performed meta-transcriptomic analysis using the RNA-sequencing dataset from the Genotype-Tissue Expression (GTEx) Project. We analyzed the 8991 RNA-sequencing data obtained from 51 somatic tissues from 547 individuals and successfully detected 39 viral species in at least one tissue. We then investigated associations between virus infection and human gene expression and human disease onset. We detected some expected relationships; for instance, hepatitis C virus infection in the liver was strongly associated with interferon-stimulated gene upregulation and pathological findings of chronic hepatitis. The presence of herpes simplex virus type 1 in one subject's brain strongly associated with immune gene expression. While torque teno virus was detected in a broad range of human tissues, it was not associated with interferon responses. Being notable in light of its association with lymphoproliferative disorders, Epstein-Barr virus infection in the spleen and blood was associated with an increase in plasma cells in healthy subjects. Human herpesvirus 7 was often detected in the stomach; intriguingly, it associated with the proportion of human leukocytes in the stomach as well as digestive gene expression. Moreover, virus infections in the local tissues associated with systemic immune responses in circulating blood.ConclusionsTo our knowledge, this study is the first comprehensive investigation of the human virome in a variety of tissues in healthy individuals through meta-transcriptomic analysis. Further investigation of the associations described here, and application of this analytical pipeline to additional datasets, will be useful to reveal the impact of viral infections on human health.

Dataset Information

A reference tissue atlas for the human kidney.

Publications

A reference tissue atlas for the human kidney.

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