Mapping systemic lupus erythematosus heterogeneity at the single-cell level

Djamel Nehar-Belaid; Seunghee Hong; Radu Marches; Guo Chen; Mohan Bolisetty; Jeanine Baisch; Lynnette Walters; Marilynn Punaro; Robert J. Rossi; Cheng Han Chung; Richie P. Huynh; Prashant Singh; William F. Flynn; Joy Ann Tabanor-Gayle; Navya Kuchipudi; Asuncion Mejias; Magalie A. Collet; Anna Lisa Lucido; Karolina Palucka; Paul Robson; Santhanam Lakshminarayanan; Octavio Ramilo; Tracey Wright; Virginia Pascual; Jacques F. Banchereau

doi:10.1038/s41590-020-0743-0

Mapping systemic lupus erythematosus heterogeneity at the single-cell level

Djamel Nehar-Belaid, Seunghee Hong, Radu Marches, Guo Chen, Mohan Bolisetty, Jeanine Baisch, Lynnette Walters, Marilynn Punaro, Robert J. Rossi, Cheng Han Chung, Richie P. Huynh, Prashant Singh, William F. Flynn, Joy Ann Tabanor-Gayle, Navya Kuchipudi, Asuncion Mejias, Magalie A. Collet, Anna Lisa Lucido, Karolina Palucka, Paul RobsonSanthanam Lakshminarayanan, Octavio Ramilo, Tracey Wright, Virginia Pascual, Jacques F. Banchereau

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171 Scopus citations

Abstract

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 ~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.

Original language	English (US)
Pages (from-to)	1094-1106
Number of pages	13
Journal	Nature immunology
Volume	21
Issue number	9
DOIs	https://doi.org/10.1038/s41590-020-0743-0
State	Published - Sep 1 2020

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Nehar-Belaid, D., Hong, S., Marches, R., Chen, G., Bolisetty, M., Baisch, J., Walters, L., Punaro, M., Rossi, R. J., Chung, C. H., Huynh, R. P., Singh, P., Flynn, W. F., Tabanor-Gayle, J. A., Kuchipudi, N., Mejias, A., Collet, M. A., Lucido, A. L., Palucka, K., ... Banchereau, J. F. (2020). Mapping systemic lupus erythematosus heterogeneity at the single-cell level. Nature immunology, 21(9), 1094-1106. https://doi.org/10.1038/s41590-020-0743-0

Nehar-Belaid, D, Hong, S, Marches, R, Chen, G, Bolisetty, M, Baisch, J, Walters, L, Punaro, M, Rossi, RJ, Chung, CH, Huynh, RP, Singh, P, Flynn, WF, Tabanor-Gayle, JA, Kuchipudi, N, Mejias, A, Collet, MA, Lucido, AL, Palucka, K, Robson, P, Lakshminarayanan, S, Ramilo, O, Wright, T, Pascual, V & Banchereau, JF 2020, 'Mapping systemic lupus erythematosus heterogeneity at the single-cell level', Nature immunology, vol. 21, no. 9, pp. 1094-1106. https://doi.org/10.1038/s41590-020-0743-0

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abstract = "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 (ISGhi) 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 ~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.",

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AU - Nehar-Belaid, Djamel

AU - Hong, Seunghee

AU - Marches, Radu

AU - Chen, Guo

AU - Bolisetty, Mohan

AU - Baisch, Jeanine

AU - Walters, Lynnette

AU - Punaro, Marilynn

AU - Rossi, Robert J.

AU - Chung, Cheng Han

AU - Huynh, Richie P.

AU - Singh, Prashant

AU - Flynn, William F.

AU - Tabanor-Gayle, Joy Ann

AU - Kuchipudi, Navya

AU - Mejias, Asuncion

AU - Collet, Magalie A.

AU - Lucido, Anna Lisa

AU - Palucka, Karolina

AU - Robson, Paul

AU - Lakshminarayanan, Santhanam

AU - Ramilo, Octavio

AU - Wright, Tracey

AU - Pascual, Virginia

AU - Banchereau, Jacques F.

PY - 2020/9/1

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N2 - 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 (ISGhi) 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 ~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.

AB - 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 (ISGhi) 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 ~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.

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Mapping systemic lupus erythematosus heterogeneity at the single-cell level

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