A reference tissue atlas for the human kidney.
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IF: 14.957
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Cited by: 18
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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.

Keywords

CODEX
Spatial Metabolomics

MeSH terms

Humans
Kidney
Kidney Diseases
Metabolomics
Proteomics
Transcriptome

Authors

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