TY - JOUR
T1 - A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys
AU - Lake, Blue B.
AU - Chen, Song
AU - Hoshi, Masato
AU - Plongthongkum, Nongluk
AU - Salamon, Diane
AU - Knoten, Amanda
AU - Vijayan, Anitha
AU - Venkatesh, Ramakrishna
AU - Kim, Eric H.
AU - Gao, Derek
AU - Gaut, Joseph
AU - Zhang, Kun
AU - Jain, Sanjay
N1 - Funding Information:
We are thankful to all the patients for their voluntary participation in the study. We thank Alex Kim in the Urology division for assistance with access to patients undergoing nephrectomy and Alma Johnson for assistance with histology. We also thank Fellows in the Department of Pathology for assistance with triaging of nephrectomy specimens. We are grateful to Mid America Transplant for their support and generosity in providing deceased donor kidneys for research. We thank the entire KPMP consortium membership for several discussions and particularly grateful for the efforts of Drs. Matthias Kretzler, Jeffrey Hodgin and Jinghui Luo in providing KPMP pilot samples from University of Michigan. We thank Charlie Alpers, Tarek Ashkar and Tissue Interrogation Sites for the planning of the pilot sample studies. A full list of consortium members appears in Supplementary Note 1. This work was partly supported by the NIH Kidney Precision Medicine Project grants NIH 1 UG3 DK114933 to K.Z. and S.J., DK085231 (S.J.) and U2CDK114886 to the central hub of the KPMP, and the Kidney Translational Research Center (KTRC) in the Division of Nephrology at the Washington University in St. Louis.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.
AB - Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.
UR - http://www.scopus.com/inward/record.url?scp=85068055615&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-10861-2
DO - 10.1038/s41467-019-10861-2
M3 - Article
C2 - 31249312
AN - SCOPUS:85068055615
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2832
ER -