학술논문
A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease
Document Type
article
Author
Victor Hugo Canela; William S. Bowen; Ricardo Melo Ferreira; Farooq Syed; James E. Lingeman; Angela R. Sabo; Daria Barwinska; Seth Winfree; Blue B. Lake; Ying-Hua Cheng; Joseph P. Gaut; Michael Ferkowicz; Kaice A. LaFavers; Kun Zhang; Fredric L. Coe; Elaine Worcester; the Kidney Precision Medicine Project; Sanjay Jain; Michael T. Eadon; James C. Williams; Tarek M. El-Achkar
Source
Nature Communications, Vol 14, Iss 1, Pp 1-17 (2023)
Subject
Language
English
ISSN
2041-1723
Abstract
Abstract Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.