A reference tissue atlas for the human kidney.

TitleA reference tissue atlas for the human kidney.
Publication TypeJournal Article
Year of Publication2022
AuthorsHansen, J, Sealfon, R, Menon, R, Eadon, MT, Lake, BB, Steck, B, Anjani, K, Parikh, S, Sigdel, TK, Zhang, G, Velickovic, D, Barwinska, D, Alexandrov, T, Dobi, D, Rashmi, P, Otto, EA, Rivera, M, Rose, MP, Anderton, CR, Shapiro, JP, Pamreddy, A, Winfree, S, Xiong, Y, He, Y, de Boer, IH, Hodgin, JB, Barisoni, L, Naik, AS, Sharma, K, Sarwal, MM, Zhang, K, Himmelfarb, J, Rovin, B, El-Achkar, TM, Laszik, Z, He, JCijiang, Dagher, PC, M Valerius, T, Jain, S, Satlin, LM, Troyanskaya, OG, Kretzler, M, Iyengar, R, Azeloglu, EU
Corporate Authors
JournalSci Adv
Volume8
Issue23
Paginationeabn4965
Date Published2022 Jun 10
ISSN2375-2548
KeywordsHumans, Kidney, Kidney Diseases, Metabolomics, Proteomics, Transcriptome
Abstract

<p>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.</p>

DOI10.1126/sciadv.abn4965
Alternate JournalSci Adv
PubMed ID35675394
PubMed Central IDPMC9176741
Grant ListUH3 DK114907 / DK / NIDDK NIH HHS / United States
UG3 DK114937 / DK / NIDDK NIH HHS / United States
U2C DK114886 / DK / NIDDK NIH HHS / United States
UH3 DK114920 / DK / NIDDK NIH HHS / United States
UH3 DK114937 / DK / NIDDK NIH HHS / United States
UG3 DK114907 / DK / NIDDK NIH HHS / United States
UH3 DK114933 / DK / NIDDK NIH HHS / United States
UH3 DK114923 / DK / NIDDK NIH HHS / United States
K23 DK125529 / DK / NIDDK NIH HHS / United States