A reference tissue atlas for the human kidney
Jens Hansen, Rachel Sealfon, Rajasree Menon, Michael T. Eadon, Blue B. Lake, Becky Steck, Kavya Anjani, Samir V. Parikh, Tara K. Sigdel, Guanshi Zhang, Dušan Veličković, Daria Barwinska, Theodore Alexandrov, Deján Dobi, Priyanka Rashmi, Edgar A. Otto, Miguel Rivera, Michael Rose, Christopher Anderton, John P. Shapiro, Annapurna Pamreddy, Seth Winfree, Yuguang Xiong, Yongqun He, Ian H. de Boer, Jeffrey B. Hodgin, Laura Barisoni, Abhijit S. Naik, Kumar Sharma, Minnie Sarwal, Kun Zhang, Jonathan Himmelfarb, Brad H. Rovin, Tarek M. El‐Achkar, Zoltán Lászik, John Cijiang He, Pierre C. Dagher, M. Todd Valerius, Sanjay Jain, Lisa M. Satlin, Olga G. Troyanskaya, Matthias Kretzler, Ravi Iyengar, Evren U. Azeloglu, Kidney Precision Medicine Project
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.