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Molecular characterization of the human kidney interstitium in health and
Barwinska D, El-Achkar TM, Ferreira RM, Syed F, Cheng YH, Winfree S, Ferkowicz
MJ, Hato T, Collins KS, Dunn KW, Kelly KJ, Sutton TA, Rovin BH, Parikh SV,
Phillips CL, Dagher PC, Eadon MT,
Submitted Externally on 2/22/2021
Volume : Pages
The gene expression signature of the human kidney interstitium is incompletely
understood. The cortical interstitium (excluding tubules, glomeruli, and
vessels) in reference nephrectomies (N = 9) and diabetic kidney biopsy specimens
(N = 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 KISS1,
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 (NOTCH3, EGFR, and HEG1) and those
down-regulated in diabetic nephropathy (MYH11, LUM, and CCDC3) were identified.
LMD transcriptomics complements snRNAseq; together, they facilitate mapping of
interstitial marker genes to aid interpretation of pathophysiology in precision
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Financial support for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
) under the MICROMouse Program, grants DK076169.
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