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

被引：346

作者：

Der, Evan ^{[1
,2
]}

Suryawanshi, Hemant ^{[3
]}

Morozov, Pavel ^{[3
]}

Kustagi, Manjunath ^{[3
]}

Goilav, Beatrice ^{[4
]}

Ranabathou, Saritha ^{[5
]}

Izmirly, Peter ^{[6
]}

Clancy, Robert ^{[6
]}

Belmont, H. Michael ^{[6
]}

Koenigsberg, Mordecai ^{[7
]}

Mokrzycki, Michele ^{[8
]}

Rominieki, Helen ^{[9
]}

Graham, Jay A. ^{[9
]}

Rocca, Juan P. ^{[9
]}

Bornkamp, Nicole ^{[6
]}

Jordan, Nicole ^{[1
,2
]}

Schulte, Emma ^{[1
,2
]}

Wu, Ming ^{[6
]}

Pullman, James ^{[10
]}

Slowikowski, Kamil ^{[11
]}

Raychaudhuri, Soumya ^{[11
]}

Guthridge, Joel ^{[12
]}

James, Judith ^{[12
]}

Buyon, Jill ^{[6
]}

Tuschl, Thomas ^{[3
]}

Putterman, Chaim ^{[1
,2
]}

Anolik, Jennifer ^{[13
,14
]}

Apruzzese, William ^{[15
,16
]}

Arazi, Arnon ^{[11
]}

Berthier, Celine ^{[17
]}

Brenner, Michael ^{[16
]}

Connery, Sean ^{[18
]}

Cunningham, Melissa ^{[16
,19
]}

Dall'Era, Maria ^{[20
]}

Davidson, Anne ^{[21
]}

Fava, Andrea ^{[22
]}

Fonseka, Chamith ^{[16
,23
,24
]}

Furie, Richard ^{[25
]}

Goldman, Dan ^{[22
]}

Gupta, Rohit ^{[26
]}

Guthridge, Joel ^{[12
]}

Hacohen, Nir

Hildeman, David ^{[27
,28
]}

Hoover, Paul

Hsu, Raymond ^{[29
]}

Kado, Ruba ^{[17
]}

Kalunian, Kenneth ^{[30
]}

Kamen, Diane

Kretzler, Mattias ^{[17
]}

Maecker, Holden ^{[31
]}

机构：

[1] Albert Einstein Coll Med, Div Rheumatol, Bronx, NY 10467 USA

[2] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA

[3] Rockefeller Univ, Lab RNA Mol Biol, 1230 York Ave, New York, NY 10021 USA

[4] Albert Einstein Coll Med, Childrens Hosp Montefiore, Pediat Nephrol, Bronx, NY 10467 USA

[5] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Pediat Nephrol, Little Rock, AR 72205 USA

[6] NYU, Sch Med, New York, NY 10016 USA

[7] Montefiore Med Ctr, Dept Radiol, 111 E 210th St, Bronx, NY 10467 USA

[8] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10467 USA

[9] Montefiore Med Ctr, Montefiore Einstein Ctr Transplantat, 111 E 210th St, Bronx, NY 10467 USA

[10] Montefiore Med Ctr, Clin Pathol, 111 E 210th St, Bronx, NY 10467 USA

[11] Broad Inst MIT & Harvard, Cambridge, MA USA

[12] Oklahoma Med Res Fdn, Oklahoma City, OK USA

[13] Univ Rochester, Med Ctr, Dept Med, Div Allergy Immunol & Rheumatol, Rochester, NY 14642 USA

[14] Univ Rochester, Med Ctr, Ctr Musculoskeletal Res, Rochester, NY 14642 USA

[15] Brigham & Womens Hosp, Div Rheumatol, Immunol, Allergy, 75 Francis St, Boston, MA 02115 USA

[16] Harvard Med Sch, Boston, MA 02115 USA

[17] Univ Michigan, Dept Nephrol, Internal Med, Ann Arbor, MI 48109 USA

[18] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Med, El Paso, TX USA

[19] Med Univ South Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA

[20] Univ Calif San Francisco, Rheumatol Div, San Francisco, CA 94143 USA

[21] Northwell Hlth, Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY USA

[22] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA

[23] Brigham & Womens Hosp, Ctr Data Sci, 75 Francis St, Boston, MA 02115 USA

[24] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA

[25] Northwell Hlth, Div Rheumatol, Great Neck, NY USA

[26] Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA

[27] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA

[28] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA

[29] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA

[30] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA

[31] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

[32] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA

[33] PLLC, Integrat Med Clin North Carolina, Chapel Hill, NC USA

[34] Stanford Univ, Dept Med, Sch Med, Div Immunol & Rheumatol, Stanford, CA 94305 USA

[35] Univ Texas Houston, Dept Internal Med, Houston, TX USA

来源：

NATURE IMMUNOLOGY | 2019年 / 20卷 / 07期

基金：

美国国家卫生研究院;

关键词：

EPITHELIAL-MYOFIBROBLAST TRANSDIFFERENTIATION; RENAL OUTCOMES; ERYTHEMATOSUS; EXPRESSION; GENE; KEGG; RECONSTRUCTION; INFLAMMATION; INTERFERON; TRANSITION;

D O I：

10.1038/s41590-019-0386-1

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：915 / +

页数：15

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