TY - JOUR
T1 - Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways
AU - the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium
AU - Der, Evan
AU - Suryawanshi, Hemant
AU - Morozov, Pavel
AU - Kustagi, Manjunath
AU - Goilav, Beatrice
AU - Ranabothu, Saritha
AU - Izmirly, Peter
AU - Clancy, Robert
AU - Belmont, H. Michael
AU - Koenigsberg, Mordecai
AU - Mokrzycki, Michele
AU - Rominieki, Helen
AU - Graham, Jay A.
AU - Rocca, Juan P.
AU - Bornkamp, Nicole
AU - Jordan, Nicole
AU - Schulte, Emma
AU - Wu, Ming
AU - Pullman, James
AU - Slowikowski, Kamil
AU - Raychaudhuri, Soumya
AU - Guthridge, Joel
AU - James, Judith
AU - Buyon, Jill
AU - Tuschl, Thomas
AU - Putterman, Chaim
AU - Anolik, Jennifer
AU - Apruzzese, William
AU - Arazi, Arnon
AU - Berthier, Celine
AU - Brenner, Michael
AU - Buyon, Jill
AU - Clancy, Robert
AU - Connery, Sean
AU - Cunningham, Melissa
AU - Dall’Era, Maria
AU - Davidson, Anne
AU - Der, Evan
AU - Fava, Andrea
AU - Fonseka, Chamith
AU - Furie, Richard
AU - Goldman, Dan
AU - Gupta, Rohit
AU - Guthridge, Joel
AU - Hacohen, Nir
AU - Hildeman, David
AU - Hoover, Paul
AU - Hsu, Raymond
AU - James, Judith
AU - Kado, Ruba
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85066092533&partnerID=8YFLogxK
U2 - 10.1038/s41590-019-0386-1
DO - 10.1038/s41590-019-0386-1
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C2 - 31110316
AN - SCOPUS:85066092533
SN - 1529-2908
VL - 20
SP - 915
EP - 927
JO - Nature Immunology
JF - Nature Immunology
IS - 7
ER -