Mapping systemic lupus erythematosus heterogeneity at the single-cell level

被引：282

作者：

Nehar-Belaid, Djamel ^{[1
]}

Hong, Seunghee ^{[2
,3
]}

Marches, Radu ^{[1
]}

Chen, Guo ^{[1
]}

Bolisetty, Mohan ^{[1
]}

Baisch, Jeanine ^{[2
,3
]}

Walters, Lynnette ^{[4
]}

Punaro, Marilynn ^{[4
,5
]}

Rossi, Robert J. ^{[1
]}

Chung, Cheng-Han ^{[1
]}

Huynh, Richie P. ^{[1
]}

Singh, Prashant ^{[1
]}

Flynn, William F. ^{[1
]}

Tabanor-Gayle, Joy-Ann ^{[6
]}

Kuchipudi, Navya ^{[6
]}

Mejias, Asuncion ^{[7
,8
]}

Collet, Magalie A. ^{[1
]}

Lucido, Anna Lisa ^{[1
]}

Palucka, Karolina ^{[1
]}

Robson, Paul ^{[1
,9
,10
]}

Lakshminarayanan, Santhanam ^{[6
]}

Ramilo, Octavio ^{[7
,8
]}

Wright, Tracey ^{[4
,5
]}

Pascual, Virginia ^{[2
,3
]}

Banchereau, Jacques F. ^{[1
]}

机构：

[1] Jackson Lab Genom Med, Farmington, CT 06032 USA

[2] Weill Cornell Med, Drukier Inst Childrens Hlth, New York, NY 10065 USA

[3] Weill Cornell Med, Dept Pediat, New York, NY 10065 USA

[4] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA

[5] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA

[6] Univ Connecticut, Sch Med, Dept Med, Farmington, CT USA

[7] Nationwide Childrens Hosp, Div Pediat Infect Dis, Columbus, OH USA

[8] Ohio State Univ, Sch Med, Columbus, OH 43210 USA

[9] Univ Connecticut, Sch Med, Inst Syst Genom, Farmington, CT USA

[10] Univ Connecticut, Sch Med, Dept Genet & Genome Sci, Farmington, CT USA

来源：

NATURE IMMUNOLOGY | 2020年 / 21卷 / 09期

关键词：

PLASMACYTOID DENDRITIC CELLS; INTERFERON; BLOOD; EXPRESSION; SUBSETS; ALPHA; ONSET; STAGE;

D O I：

10.1038/s41590-020-0743-0

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Patients with systemic lupus erythematosus (SLE) display a complex blood transcriptome whose cellular origin is poorly resolved. Using single-cell RNA sequencing, we profiled -276,000 peripheral blood mononuclear cells from 33 children with SLE with different degrees of disease activity and 11 matched controls. Increased expression of interferon-stimulated genes (ISGs) distinguished cells from children with SLE from healthy control cells. The high ISG expression signature (ISG(hi)) derived from a small number of transcriptionally defined subpopulations within major cell types, including monocytes, CD4(+) and CD8(+) T cells, natural killer cells, conventional and plasmacytoid dendritic cells, B cells and especially plasma cells. Expansion of unique subpopulations enriched in ISGs and/or in monogenic lupus-associated genes classified patients with the highest disease activity. Profiling of similar to 82,000 single peripheral blood mononuclear cells from adults with SLE confirmed the expansion of similar subpopulations in patients with the highest disease activity. This study lays the groundwork for resolving the origin of the SLE transcriptional signatures and the disease heterogeneity towards precision medicine applications.

引用

页码：1094 / +

页数：34

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