A reference tissue atlas for the human kidney.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
10 06 2022
10 06 2022
Historique:
entrez:
8
6
2022
pubmed:
9
6
2022
medline:
11
6
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35675394
doi: 10.1126/sciadv.abn4965
pmc: PMC9176741
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabn4965Subventions
Organisme : NIDDK NIH HHS
ID : K23 DK125529
Pays : United States
Organisme : NIDDK NIH HHS
ID : U2C DK114886
Pays : United States
Organisme : NHLBI NIH HHS
ID : U54 HL145608
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079312
Pays : United States
Organisme : NIDDK NIH HHS
ID : UG3 DK114907
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114933
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK114886
Pays : United States
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