@article{10.1172/jci.insight.133267, author = {Rajasree Menon AND Edgar A. Otto AND Paul Hoover AND Sean Eddy AND Laura Mariani AND Bradley Godfrey AND Celine C. Berthier AND Felix Eichinger AND Lalita Subramanian AND Jennifer Harder AND Wenjun Ju AND Viji Nair AND Maria Larkina AND Abhijit S. Naik AND Jinghui Luo AND Sanjay Jain AND Rachel Sealfon AND Olga Troyanskaya AND Nir Hacohen AND Jeffrey B. Hodgin AND Matthias Kretzler AND Kidney Precision Medicine Project (KPMP) AND Nephrotic Syndrome Study Network (NEPTUNE)}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Single cell transcriptomics identifies focal segmental glomerulosclerosis remission endothelial biomarker}, year = {2020}, month = {3}, volume = {5}, url = {https://insight.jci.org/articles/view/133267}, 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.}, number = {6}, doi = {10.1172/jci.insight.133267}, url = {https://doi.org/10.1172/jci.insight.133267}, }