Single cell transcriptomics identifies focal segmental glomerulosclerosis remission endothelial biomarker. Author Rajasree Menon, Edgar Otto, Paul Hoover, Sean Eddy, Laura Mariani, Bradley Godfrey, Celine Berthier, Felix Eichinger, Lalita Subramanian, Jennifer Harder, Wenjun Ju, Viji Nair, Maria Larkina, Abhijit Naik, Jinghui Luo, Sanjay Jain, Rachel Sealfon, Olga Troyanskaya, Nir Hacohen, Jeffrey Hodgin, Matthias Kretzler, Kidney Kpmp, Nephrotic Network Publication Year 2020 Type Journal Article Abstract 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. Journal JCI Insight Volume 5 Issue 6 Date Published 03/2020 ISSN Number 2379-3708 DOI 10.1172/jci.insight.133267 Alternate Journal JCI Insight PMID 32107344 PubMedGoogle ScholarBibTeXEndNote X3 XML