Single cell transcriptomics identifies focal segmental glomerulosclerosis remission endothelial biomarker.

TitleSingle cell transcriptomics identifies focal segmental glomerulosclerosis remission endothelial biomarker.
Publication TypeJournal Article
Year of Publication2020
AuthorsMenon, R, Otto, EA, Hoover, P, Eddy, S, Mariani, L, Godfrey, B, Berthier, CC, Eichinger, F, Subramanian, L, Harder, J, Ju, W, Nair, V, Larkina, M, Naik, AS, Luo, J, Jain, S, Sealfon, R, Troyanskaya, O, Hacohen, N, Hodgin, JB, Kretzler, M, Kpmp, KPrecision
Corporate Authors
JournalJCI Insight
Volume5
Issue6
Date Published2020 Mar 26
ISSN2379-3708
Abstract

<p>To define cellular mechanisms underlying kidney function and failure, the KPMP analyzes biopsy tissue in a multicenter research network to build cell-level process maps of the kidney. This study aimed to establish a single cell RNA sequencing strategy to use cell-level transcriptional profiles from kidney biopsies in KPMP to define molecular subtypes in glomerular diseases. Using multiple sources of adult human kidney reference tissue samples, 22,268 single cell profiles passed KPMP quality control parameters. Unbiased clustering resulted in 31 distinct cell clusters that were linked to kidney and immune cell types using specific cell markers. Focusing on endothelial cell phenotypes, in silico and in situ hybridization methods assigned 3 discrete endothelial cell clusters to distinct renal vascular beds. Transcripts defining glomerular endothelial cells (GEC) were evaluated in biopsies from patients with 10 different glomerular diseases in the NEPTUNE and European Renal cDNA Bank (ERCB) cohort studies. Highest GEC scores were observed in patients with focal segmental glomerulosclerosis (FSGS). Molecular endothelial signatures suggested 2 distinct FSGS patient subgroups with α-2 macroglobulin (A2M) as a key downstream mediator of the endothelial cell phenotype. Finally, glomerular A2M transcript levels associated with lower proteinuria remission rates, linking endothelial function with long-term outcome in FSGS.</p>

DOI10.1172/jci.insight.133267
Alternate JournalJCI Insight
PubMed ID32107344
PubMed Central IDPMC7213795
Grant ListUH3 DK114907 / DK / NIDDK NIH HHS / United States
UG3 DK114933 / DK / NIDDK NIH HHS / United States
U2C DK114886 / DK / NIDDK NIH HHS / United States
R24 DK082841 / DK / NIDDK NIH HHS / United States
P30 DK081943 / DK / NIDDK NIH HHS / United States
UH3 DK114933 / DK / NIDDK NIH HHS / United States