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The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline

ABSTRACT: The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline

PROVIDER: PRJNA636783 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11908518.fastq.gz	Fastqsanger.gz
	SRR11908519.fastq.gz	Fastqsanger.gz
	SRR11908520.fastq.gz	Fastqsanger.gz
	SRR11908521.fastq.gz	Fastqsanger.gz
	SRR11908522.fastq.gz	Fastqsanger.gz

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The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline.

Project description:The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline.

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The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline.

Project description:Clinical sepsis is a highly 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 and spatial transcriptomics revealed the involvement of various cell populations in injury and repair to be temporally organized and highly orchestrated. We identified key changes in gene expression that altered cellular functions and can explain features of clinical sepsis. These changes converged towards a remarkable global cell-cell communication failure and organ shutdown at a well-defined point in the sepsis timeline. Importantly, this time point was also a transition towards the emergence of recovery pathways. This rigorous spatial and temporal definition of murine sepsis will uncover precise biomarkers and targets that can help stage and treat human sepsis.

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The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline.

Project description: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.

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