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Molecular characterization of the human kidney interstitium in health and disease.

Citation
Barwinska, D., et al. “Molecular Characterization Of The Human Kidney Interstitium In Health And Disease.”. Science Advances.
Center Indiana University
Author Daria Barwinska, Tarek M El-Achkar, Ricardo Melo Ferreira, Farooq Syed, Ying-Hua Cheng, Seth Winfree, Michael J Ferkowicz, Takashi Hato, Kimberly S Collins, Kenneth W Dunn, Katherine J Kelly, Timothy A Sutton, Brad H Rovin, Samir Parikh V, Carrie L Phillips, Pierre C Dagher, Michael T Eadon, Kidney Precision Medicine Project
Abstract

The gene expression signature of the human kidney interstitium is incompletely understood. The cortical interstitium (excluding tubules, glomeruli, and vessels) in reference nephrectomies ( = 9) and diabetic kidney biopsy specimens ( = 6) was laser microdissected (LMD) and sequenced. Samples underwent RNA sequencing. Gene signatures were deconvolved using single nuclear RNA sequencing (snRNAseq) data derived from overlapping specimens. Interstitial LMD transcriptomics uncovered previously unidentified markers including , validated with in situ hybridization. LMD transcriptomics and snRNAseq revealed strong correlation of gene expression within corresponding kidney regions. Relevant enriched interstitial pathways included G-protein coupled receptor. binding and collagen biosynthesis. The diabetic interstitium was enriched for extracellular matrix organization and small-molecule catabolism. Cell type markers with unchanged expression (, , and ) and those down-regulated in diabetic nephropathy (, , and ) were identified. LMD transcriptomics complements snRNAseq; together, they facilitate mapping of interstitial marker genes to aid interpretation of pathophysiology in precision medicine studies.

Year of Publication
2021
Journal
Science advances
Volume
7
Issue
7
Date Published
12/2021
ISSN Number
2375-2548
DOI
10.1126/sciadv.abd3359
Alternate Journal
Sci Adv
PMID
33568476
PMCID
PMC7875540
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