An immune-cell signature of bacterial sepsis
Dysregulation of the immune response to bacterial infection can lead to sepsis, a condition with high mortality. Multiple whole-blood gene-expression studies have defined sepsis-associated molecular signatures, but have not resolved changes in transcriptional states of specific cell types. Here, we...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/125914 |
| _version_ | 1826215162796834816 |
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| author | Reyes, Miguel Filbin, Michael R. Bhattacharyya, Roby P. Billman, Kianna Eisenhaure, Thomas Hung, Deborah T. Levy, Bruce D. Baron, Rebecca M. Blainey, Paul C Goldberg, Marcia B. Hacohen, Nir |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Reyes, Miguel Filbin, Michael R. Bhattacharyya, Roby P. Billman, Kianna Eisenhaure, Thomas Hung, Deborah T. Levy, Bruce D. Baron, Rebecca M. Blainey, Paul C Goldberg, Marcia B. Hacohen, Nir |
| author_sort | Reyes, Miguel |
| collection | MIT |
| description | Dysregulation of the immune response to bacterial infection can lead to sepsis, a condition with high mortality. Multiple whole-blood gene-expression studies have defined sepsis-associated molecular signatures, but have not resolved changes in transcriptional states of specific cell types. Here, we used single-cell RNA-sequencing to profile the blood of people with sepsis (n = 29) across three clinical cohorts with corresponding controls (n = 36). We profiled total peripheral blood mononuclear cells (PBMCs, 106,545 cells) and dendritic cells (19,806 cells) across all subjects and, on the basis of clustering of their gene-expression profiles, defined 16 immune-cell states. We identified a unique CD14+ monocyte state that is expanded in people with sepsis and validated its power in distinguishing these individuals from controls using public transcriptomic data from subjects with different disease etiologies and from multiple geographic locations (18 cohorts, n = 1,467 subjects). We identified a panel of surface markers for isolation and quantification of the monocyte state and characterized its epigenomic and functional phenotypes, and propose a model for its induction from human bone marrow. This study demonstrates the utility of single-cell genomics in discovering disease-associated cytologic signatures and provides insight into the cellular basis of immune dysregulation in bacterial sepsis. |
| first_indexed | 2024-09-23T16:17:34Z |
| format | Article |
| id | mit-1721.1/125914 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:17:34Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1259142022-09-29T19:27:43Z An immune-cell signature of bacterial sepsis Reyes, Miguel Filbin, Michael R. Bhattacharyya, Roby P. Billman, Kianna Eisenhaure, Thomas Hung, Deborah T. Levy, Bruce D. Baron, Rebecca M. Blainey, Paul C Goldberg, Marcia B. Hacohen, Nir Massachusetts Institute of Technology. Department of Biological Engineering Broad Institute of MIT and Harvard Dysregulation of the immune response to bacterial infection can lead to sepsis, a condition with high mortality. Multiple whole-blood gene-expression studies have defined sepsis-associated molecular signatures, but have not resolved changes in transcriptional states of specific cell types. Here, we used single-cell RNA-sequencing to profile the blood of people with sepsis (n = 29) across three clinical cohorts with corresponding controls (n = 36). We profiled total peripheral blood mononuclear cells (PBMCs, 106,545 cells) and dendritic cells (19,806 cells) across all subjects and, on the basis of clustering of their gene-expression profiles, defined 16 immune-cell states. We identified a unique CD14+ monocyte state that is expanded in people with sepsis and validated its power in distinguishing these individuals from controls using public transcriptomic data from subjects with different disease etiologies and from multiple geographic locations (18 cohorts, n = 1,467 subjects). We identified a panel of surface markers for isolation and quantification of the monocyte state and characterized its epigenomic and functional phenotypes, and propose a model for its induction from human bone marrow. This study demonstrates the utility of single-cell genomics in discovering disease-associated cytologic signatures and provides insight into the cellular basis of immune dysregulation in bacterial sepsis. 2020-06-22T15:59:53Z 2020-06-22T15:59:53Z 2020-02 2019-12 2020-06-19T13:44:35Z Article http://purl.org/eprint/type/JournalArticle 1078-8956 1546-170X https://hdl.handle.net/1721.1/125914 Reyes, Miguel et al. "An immune-cell signature of bacterial sepsis." Nature Medicine 26, 3 (February 2020): 333–340 © 2020 The Author(s) en http://dx.doi.org/10.1038/s41591-020-0752-4 Nature Medicine Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC Prof. Blainey via Howard Silver |
| spellingShingle | Reyes, Miguel Filbin, Michael R. Bhattacharyya, Roby P. Billman, Kianna Eisenhaure, Thomas Hung, Deborah T. Levy, Bruce D. Baron, Rebecca M. Blainey, Paul C Goldberg, Marcia B. Hacohen, Nir An immune-cell signature of bacterial sepsis |
| title | An immune-cell signature of bacterial sepsis |
| title_full | An immune-cell signature of bacterial sepsis |
| title_fullStr | An immune-cell signature of bacterial sepsis |
| title_full_unstemmed | An immune-cell signature of bacterial sepsis |
| title_short | An immune-cell signature of bacterial sepsis |
| title_sort | immune cell signature of bacterial sepsis |
| url | https://hdl.handle.net/1721.1/125914 |
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