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| Status |
Public on Mar 03, 2021 |
| Title |
Dynamic changes in human single cell transcriptional signatures during fatal sepsis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Systemic infections, especially in patients with chronic diseases, result in sepsis: an explosive, uncoordinated immune response that can lead to multisystem organ failure with a high mortality rate. Sepsis survivors and non-survivors oftentimes have similar clinical phenotypes or sepsis biomarker expression upon diagnosis, suggesting that the dynamics of sepsis in the critical early stage may have an impact on these opposite outcomes. To investigate this, we designed a within-subject study of patients with systemic gram-negative bacterial sepsis with surviving and fatal outcomes and performed single-cell transcriptomic analyses of peripheral blood mononuclear cells (PBMC) collected during the critical period between sepsis recognition and 6 hours. We observed that the largest sepsis-induced expression changes over time in surviving versus fatal sepsis were in CD14+ monocytes, including gene signatures previously reported for sepsis outcomes. We further identify changes in the metabolic pathways of both monocytes and platelets, the emergence of erythroid precursors, and T cell exhaustion signatures, with the most extreme differences occurring between the non-sepsis control and the sepsis non-survivor. Our single-cell observations are consistent with trends from public datasets but also reveal specific effects in individual immune cell populations, which change within hours. In conclusion, this pilot study provides the first single-cell results with a repeated measures design in sepsis to analyze the temporal changes in the immune cell population behavior in surviving or fatal sepsis. These findings indicate that tracking temporal expression changes in specific cell-types could lead to more accurate predictions of sepsis outcomes. We also identify molecular pathways that could be therapeutically controlled to improve the sepsis trajectory toward better outcomes.
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| Overall design |
Single-cell RNA-sequencing of human peripheral blood mononuclear cells from heathy controls, survivor and non-survivor of gram-negative sepsis patients.
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| Contributor(s) |
Qiu X, Li J, Bonenfant J, Jaroszewski L, Klein W, Godzik A, Nair MG |
| Citation(s) |
34558746 |
| Submission date |
Feb 23, 2021 |
| Last update date |
Dec 31, 2023 |
| Contact name |
Xinru Qiu |
| E-mail(s) |
xqiu014@ucr.edu
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| Organization name |
University of California, Riverside
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| Department |
School of Medicine
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| Lab |
Godzik
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| Street address |
109 Picnic Hill Rd
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| City |
RIVERSIDE |
| State/province |
CA |
| ZIP/Postal code |
92507 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA704394 |
| SRA |
SRP307774 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE167363_RAW.tar |
321.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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