HCA Data Explorer

Dynamic changes in human single cell transcriptional signatures during fatal sepsis

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Updated May 16, 2023

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. Summary sentence Single cell transcriptomics of peripheral blood mononuclear cells in surviving and fatal sepsis reveal inflammatory and metabolic pathways that change within hours of sepsis recognition.

Xinru QiuUniversity of California Riversidexqiu014@ucr.edu
Xinru Qiu1
Jiang Li1
Jeff Bonenfant2
Lukasz Jaroszewski1
Walter Klein3
Adam Godzik (Principal Investigator)1
Meera Nair1
1University of California Riverside
2 Riverside University Health System Medical Center
3Riverside University Health System Medical Center
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To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/8b954fb2-bccb-44c5-84e3-9f91e9189c40
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GEO Series Accessions:

Analysis Portals

None

Project Label

HumanPBMCfatalSepsis

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

blood

Organ Part

Unspecified

Selected Cell Types

peripheral blood mononuclear cell

Disease Status (Specimen)

2 disease statuses

Disease Status (Donor)

2 disease statuses

Development Stage

human adult stage

Library Construction Method

10x 3' v3

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

analysis_protocol_1

File Format

3 file formats

Cell Count Estimate

27.7k

Donor Count

7
fastq.gz24 file(s)tar1 file(s)xlsx1 file(s)