A reference tissue atlas for the human kidney. Author Jens Hansen, Rachel Sealfon, Rajasree Menon, Michael Eadon, Blue Lake, Becky Steck, Kavya Anjani, Samir Parikh, Tara Sigdel, Guanshi Zhang, Dusan Velickovic, Daria Barwinska, Theodore Alexandrov, Dejan Dobi, Priyanka Rashmi, Edgar Otto, Miguel Rivera, Michael Rose, Christopher Anderton, John Shapiro, Annapurna Pamreddy, Seth Winfree, Yuguang Xiong, Yongqun He, Ian de Boer, Jeffrey Hodgin, Laura Barisoni, Abhijit Naik, Kumar Sharma, Minnie Sarwal, Kun Zhang, Jonathan Himmelfarb, Brad Rovin, Tarek El-Achkar, Zoltan Laszik, John He, Pierre Dagher, M Todd Valerius, Sanjay Jain, Lisa Satlin, Olga Troyanskaya, Matthias Kretzler, Ravi Iyengar, Evren Azeloglu, Kidney Precision Medicine Project Publication Year 2022 Type Journal Article 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. Keywords Humans, Proteomics, Transcriptome, Metabolomics, Kidney, Kidney Diseases Journal Sci Adv Volume 8 Issue 23 Pages eabn4965 Date Published 2022 Jun 10 ISSN Number 2375-2548 DOI 10.1126/sciadv.abn4965 Alternate Journal Sci Adv PMCID PMC9176741 PMID 35675394 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML