The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
An immune-cell signature of bacterial sepsis
Open accessAbstract
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. Single-cell transcriptomic analysis identifies a distinct gene signature associated with peripheral monocyte populations that distinguishes people with sepsis from those with sterile inflammation and uninfected controls.
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Metadata
- Authors
- Reyes, M., Filbin, M. R., Bhattacharyya, R. P., Billman, K., Eisenhaure, T., Hung, D. T., Levy, B. D., Baron, R. M., Blainey, P. C., Goldberg, M. B., & Hacohen, N.
- Venue
- Nature Medicine
- Published
- 2020-02-17
- Volume
- 26
- Issue
- 3
- Pages
- 333-340
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3006033724
- Cited by
- 489
- References
- 52
- FWCI
- 35.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- Licence
- www.springer.com/tdm (tdm)
- www.springer.com/tdm (vor)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (U24AI118668)
- David P. Ryan, MD Endowed Chair in Cancer Research
- U.S. Department of Health & Human Services | National Institutes of Health (1K08AI119157-04)
- U.S. Department of Health & Human Services | Biomedical Advanced Research and Development Authority (1DSEP160030-01-00)
- Burroughs Wellcome Fund
- Allergan Foundation
- Broad Institute
- Ellison Foundation
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- Reyes, M., Filbin, M. R., Bhattacharyya, R. P., Billman, K., Eisenhaure, T., Hung, D. T., Levy, B. D., Baron, R. M., Blainey, P. C., Goldberg, M. B., & Hacohen, N. (2020). An immune-cell signature of bacterial sepsis. Nature Medicine. https://doi.org/10.1038/s41591-020-0752-4
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
