Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis

Evan Der, Saritha Ranabothu, Hemant Suryawanshi, Kemal M. Akat, Robert Clancy, Pavel Morozov, Manjunath Kustagi, Mareike Czuppa, Peter Izmirly, H. Michael Belmont, Tao Wang, Nicole Jordan, Nicole Bornkamp, Janet Nwaukoni, July Martinez, Beatrice Goilav, Jill P. Buyon, Thomas Tuschl, Chaim Putterman

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Lupus nephritis is a leading cause of mortality among systemic lupus erythematosus (SLE) patients, and its heterogeneous nature poses a significant challenge to the development of effective diagnostics and treatments. Single cell RNA sequencing (scRNA-seq) offers a potential solution to dissect the heterogeneity of the disease and enables the study of similar cell types distant from the site of renal injury to identify novel biomarkers. We applied scRNA-seq to human renal and skin biopsy tissues and demonstrated that scRNA-seq can be performed on samples obtained during routine care. Chronicity index, IgG deposition, and quantity of proteinuria correlated with a transcriptomic-based score composed of IFN-inducible genes in renal tubular cells. Furthermore, analysis of cumulative expression profiles of single cell keratinocytes dissociated from nonlesional, non-sun-exposed skin of patients with lupus nephritis also revealed upregulation of IFN-inducible genes compared with keratinocytes isolated from healthy controls. This indicates the possible use of scRNA-seq analysis of skin biopsies as a biomarker of renal disease. These data support the potential utility of scRNA-seq to provide new insights into the pathogenesis of lupus nephritis and pave the way for exploiting a readily accessible tissue to reflect injury in the kidney.

Original languageEnglish (US)
JournalJCI insight
Volume2
Issue number9
DOIs
StatePublished - May 4 2017

Fingerprint

RNA Sequence Analysis
Lupus Nephritis
Kidney
Keratinocytes
Skin
Biomarkers
Biopsy
Wounds and Injuries
Proteinuria
Systemic Lupus Erythematosus
Genes
Up-Regulation
Immunoglobulin G
Mortality

Keywords

  • Nephrology

Cite this

Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis. / Der, Evan; Ranabothu, Saritha; Suryawanshi, Hemant; Akat, Kemal M.; Clancy, Robert; Morozov, Pavel; Kustagi, Manjunath; Czuppa, Mareike; Izmirly, Peter; Belmont, H. Michael; Wang, Tao; Jordan, Nicole; Bornkamp, Nicole; Nwaukoni, Janet; Martinez, July; Goilav, Beatrice; Buyon, Jill P.; Tuschl, Thomas; Putterman, Chaim.

In: JCI insight, Vol. 2, No. 9, 04.05.2017.

Research output: Contribution to journalArticle

Der, E, Ranabothu, S, Suryawanshi, H, Akat, KM, Clancy, R, Morozov, P, Kustagi, M, Czuppa, M, Izmirly, P, Belmont, HM, Wang, T, Jordan, N, Bornkamp, N, Nwaukoni, J, Martinez, J, Goilav, B, Buyon, JP, Tuschl, T & Putterman, C 2017, 'Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis', JCI insight, vol. 2, no. 9. https://doi.org/10.1172/jci.insight.93009
Der E, Ranabothu S, Suryawanshi H, Akat KM, Clancy R, Morozov P et al. Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis. JCI insight. 2017 May 4;2(9). https://doi.org/10.1172/jci.insight.93009
Der, Evan ; Ranabothu, Saritha ; Suryawanshi, Hemant ; Akat, Kemal M. ; Clancy, Robert ; Morozov, Pavel ; Kustagi, Manjunath ; Czuppa, Mareike ; Izmirly, Peter ; Belmont, H. Michael ; Wang, Tao ; Jordan, Nicole ; Bornkamp, Nicole ; Nwaukoni, Janet ; Martinez, July ; Goilav, Beatrice ; Buyon, Jill P. ; Tuschl, Thomas ; Putterman, Chaim. / Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis. In: JCI insight. 2017 ; Vol. 2, No. 9.
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