A reference tissue atlas for the human kidney

Jens Hansen(Icahn School of Medicine at Mount Sinai), Rachel Sealfon(Princeton University), Rajasree Menon(University of Michigan), Michael T. Eadon(Indiana University School of Medicine), Blue B. Lake(University of California San Diego), Becky Steck(University of Michigan), Kavya Anjani(University of California, San Francisco), Samir V. Parikh(The Ohio State University), Tara K. Sigdel(University of California, San Francisco), Guanshi Zhang(The University of Texas at San Antonio Health Science Center), Dušan Veličković(Pacific Northwest National Laboratory), Daria Barwinska(Indiana University School of Medicine), Theodore Alexandrov(European Molecular Biology Laboratory), Deján Dobi(University of California, San Francisco), Priyanka Rashmi(University of California, San Francisco), Edgar A. Otto(University of Michigan), Miguel Rivera(University of California, San Francisco), Michael Rose(University of Michigan), Christopher Anderton(Pacific Northwest National Laboratory), John P. Shapiro(The Ohio State University), Annapurna Pamreddy(The University of Texas at San Antonio Health Science Center), Seth Winfree(Indiana University School of Medicine), Yuguang Xiong(Icahn School of Medicine at Mount Sinai), Yongqun He(University of Michigan), Ian H. de Boer(University of Washington), Jeffrey B. Hodgin(University of Michigan), Laura Barisoni(Duke University), Abhijit S. Naik(University of Michigan), Kumar Sharma(The University of Texas at San Antonio Health Science Center), Minnie Sarwal(University of California, San Francisco), Kun Zhang(University of California San Diego), Jonathan Himmelfarb(University of Washington), Brad H. Rovin(The Ohio State University), Tarek M. El‐Achkar(Indiana University School of Medicine), Zoltán Lászik(University of California, San Francisco), John Cijiang He(Icahn School of Medicine at Mount Sinai), Pierre C. Dagher(Indiana University School of Medicine), M. Todd Valerius(Brigham and Women's Hospital), Sanjay Jain(Washington University in St. Louis), Lisa M. Satlin(Icahn School of Medicine at Mount Sinai), Olga G. Troyanskaya(Princeton University), Matthias Kretzler(University of Michigan), Ravi Iyengar(Icahn School of Medicine at Mount Sinai), Evren U. Azeloglu(Icahn School of Medicine at Mount Sinai), Kidney Precision Medicine Project
Science Advances
June 8, 2022
10.1126/sciadv.abn4965
Cited by 169Open Access
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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.

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