TY - JOUR
T1 - A reference tissue atlas for the human kidney
AU - Kidney Precision Medicine Project
AU - Hansen, Jens
AU - Sealfon, Rachel
AU - Menon, Rajasree
AU - Eadon, Michael T.
AU - Lake, Blue B.
AU - Steck, Becky
AU - Anjani, Kavya
AU - Parikh, Samir
AU - Sigdel, Tara K.
AU - Zhang, Guanshi
AU - Velickovic, Dusan
AU - Barwinska, Daria
AU - Alexandrov, Theodore
AU - Dobi, Dejan
AU - Rashmi, Priyanka
AU - Otto, Edgar A.
AU - Rivera, Miguel
AU - Rose, Michael P.
AU - Anderton, Christopher R.
AU - Shapiro, John P.
AU - Pamreddy, Annapurna
AU - Winfree, Seth
AU - Xiong, Yuguang
AU - He, Yongqun
AU - de Boer, Ian H.
AU - Hodgin, Jeffrey B.
AU - Barisoni, Laura
AU - Naik, Abhijit S.
AU - Sharma, Kumar
AU - Sarwal, Minnie M.
AU - Zhang, Kun
AU - Himmelfarb, Jonathan
AU - Rovin, Brad
AU - El-Achkar, Tarek M.
AU - Laszik, Zoltan
AU - He, John Cijiang
AU - Dagher, Pierre C.
AU - Todd Valerius, M.
AU - Jain, Sanjay
AU - Satlin, Lisa M.
AU - Troyanskaya, Olga G.
AU - Kretzler, Matthias
AU - Iyengar, Ravi
AU - Azeloglu, Evren U.
N1 - Funding Information:
KPMP acknowledges all the participants, patients, and the scientific officers from the National Institute of Diabetes and Digestive and Kidney Diseases. KPMP was supported by NIH grants UH3 DK114923, UH3 DK114920, UH3 DK114933, UH3 DK114937, UH3 DK114907, and U2C DK114886. A complete list of all KPMP members can be found at kpmp.org. We thank J. Goldfarb for critically reading of the manuscript.
Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved;
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85131772384&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abn4965
DO - 10.1126/sciadv.abn4965
M3 - Article
C2 - 35675394
AN - SCOPUS:85131772384
SN - 2375-2548
VL - 8
JO - Science Advances
JF - Science Advances
IS - 23
M1 - eabn4965
ER -