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The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline
- Source :
- eLife, eLife, Vol 10 (2021)
- Publication Year :
- 2021
- Publisher :
- eLife Sciences Publications, Ltd, 2021.
-
Abstract
- Sepsis is a dynamic state that progresses at variable rates and has life-threatening consequences. Staging patients along the sepsis timeline requires a thorough knowledge of the evolution of cellular and molecular events at the tissue level. Here, we investigated the kidney, an organ central to the pathophysiology of sepsis. Single-cell RNA-sequencing in a murine endotoxemia model revealed the involvement of various cell populations to be temporally organized and highly orchestrated. Endothelial and stromal cells were the first responders. At later time points, epithelial cells upregulated immune-related pathways while concomitantly downregulating physiological functions such as solute homeostasis. Sixteen hours after endotoxin, there was global cell–cell communication failure and organ shutdown. Despite this apparent organ paralysis, upstream regulatory analysis showed significant activity in pathways involved in healing and recovery. This rigorous spatial and temporal definition of murine endotoxemia will uncover precise biomarkers and targets that can help stage and treat human sepsis.
- Subjects :
- 0301 basic medicine
Male
Mouse
Cell
030232 urology & nephrology
Bioinformatics
Kidney
sepsis
Mice
0302 clinical medicine
Immunology and Inflammation
Medicine
Biology (General)
single-cell RNA-seq
General Neuroscience
Acute kidney injury
General Medicine
Middle Aged
medicine.anatomical_structure
acute kidney injury
medicine.symptom
Research Article
Human
Adult
Stromal cell
QH301-705.5
Science
Inflammation
General Biochemistry, Genetics and Molecular Biology
Sepsis
03 medical and health sciences
Young Adult
Downregulation and upregulation
Animals
Humans
Aged
General Immunology and Microbiology
business.industry
Gene Expression Profiling
medicine.disease
Endotoxemia
Mice, Inbred C57BL
Endotoxins
030104 developmental biology
business
Homeostasis
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....fd7ca35f3fcce6c4263a0c273709fab3