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Nat Immunol. 2019 May 20. doi: 10.1038/s41590-019-0386-1. [Epub ahead of print]

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

Author information

1
Division of Rheumatology and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
2
Laboratory for RNA Molecular Biology, The Rockefeller University, New York, New York, USA.
3
Pediatric Nephrology, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, USA.
4
Pediatric Nephrology, Arkansas Children's Hospital, University of Arkansas Medical Sciences, Little Rock, Arkansas, USA.
5
New York University School of Medicine, New York, New York, USA.
6
Department of Radiology, Montefiore Medical Center, Bronx, New York, USA.
7
Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.
8
Montefiore Einstein Center for Transplantation, Montefiore Medical Center, Bronx, New York, USA.
9
Clinical Pathology, Montefiore Medical Center, Bronx, New York, USA.
10
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
11
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
12
New York University School of Medicine, New York, New York, USA. jill.buyon@nyumc.org.
13
Laboratory for RNA Molecular Biology, The Rockefeller University, New York, New York, USA. ttuschl@mail.rockefeller.edu.
14
Division of Rheumatology and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA. chaim.putterman@einstein.yu.edu.

Abstract

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.

PMID:
31110316
DOI:
10.1038/s41590-019-0386-1

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