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Species: human
Number of cells: 6142
Study size: 395MB

skin 

Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways

Evan Der, Hemant Suryawanshi, Pavel Morozov, Manjunath Kustagi, Beatrice Goilav, Saritha Ranabothu, Peter Izmirly, Robert Clancy, H. Michael Belmont, Mordecai Koenigsberg, Michele Mokrzycki, Helen Rominieki, Jay A. Graham, Juan P. Rocca, Nicole Bornkamp, Nicole Jordan, Emma Schulte, Ming Wu, James Pullman, Kamil Slowikowski, Soumya Raychaudhuri, Joel Guthridge, Judith James, Jill Buyon, Thomas Tuschl, Chaim Putterman, the Accelerating Medicines Partnership Rheumatoid Arthritis, Systemic Lupus Erythematosus (AMP RA/SLE) Consortium

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.

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