Urine single cell RNA-sequencing in focal segmental glomerulosclerosis reveals inflammatory signatures in immune cells and podocytes

Latt, K. Z.; Heymann, J.; Jessee, J. H.; Rosenberg, A. Z.; Berthier, C. C.; Eddy, S.; Yoshida, T.; Zhao, Y.; Chen, V.; Nelson, G. W.; Cam, M.; Kumar, P.; Mehta, M.; Kelly, M. C.; Kretzler, M.; The Nephrotic Syndrome Study Network (NEPTUNE),; The Accelerating Medicines Partnership in RA and SLE (AMP RA/SLE) consortium,; Winkler, C. A.; Kopp, J. B.

doi:10.1101/2020.10.18.343285

bioRxiv · 10.1101/2020.10.18.343285

Urine single cell RNA-sequencing in focal segmental glomerulosclerosis reveals inflammatory signatures in immune cells and podocytes

Latt, K. Z.·Heymann, J.·Jessee, J. H.·Rosenberg, A. Z.·Berthier, C. C.·Eddy, S.·Yoshida, T.·Zhao, Y.·Chen, V.·Nelson, G. W.·Cam, M.·Kumar, P.·Mehta, M.·Kelly, M. C.·Kretzler, M.·The Nephrotic Syndrome Study Network (NEPTUNE),·The Accelerating Medicines Partnership in RA and SLE (AMP RA/SLE) consortium,·Winkler, C. A.·Kopp, J. B.

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Abstract

The diagnosis of focal segmental glomerulosclerosis (FSGS) requires a renal biopsy, which is invasive and can be problematic in children and in some adults. We used single cell RNA-sequencing to explore disease-related cellular signatures in 23 urine samples from 12 FSGS subjects. We identified immune cells, predominantly monocytes, and renal epithelial cells, including podocytes. Analysis revealed M1 and M2 monocyte subsets, and podocytes showing high expression of genes for epithelial-to-mesenchymal transition (EMT). We confirmed M1 and M2 gene signatures using published monocyte/macrophage data from lupus nephritis and cancer. Using renal transcriptomic data from the Nephrotic Syndrome Study Network (NEPTUNE), we found that urine cell immune and EMT signature genes showed higher expression in FSGS biopsies compared to minimal change disease biopsies. These results suggest that urine cell profiling may serve as a diagnostic and prognostic tool in nephrotic syndrome and aid in identifying novel biomarkers and developing personalized therapeutic strategies.

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Latt, K. Z., Heymann, J., Jessee, J. H., Rosenberg, A. Z., Berthier, C. C., Eddy, S., Yoshida, T., Zhao, Y., Chen, V., Nelson, G. W., Cam, M., Kumar, P., Mehta, M., Kelly, M. C., Kretzler, M., The Nephrotic Syndrome Study Network (NEPTUNE),, The Accelerating Medicines Partnership in RA and SLE (AMP RA/SLE) consortium,, Winkler, C. A., Kopp, J. B.. 2020-10-19. Urine single cell RNA-sequencing in focal segmental glomerulosclerosis reveals inflammatory signatures in immune cells and podocytes. https://doi.org/10.1101/2020.10.18.343285

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