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.

中文翻译：

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肾脏对内毒素的精心安排的细胞和分子反应定义了精确的脓毒症时间表

脓毒症是一种动态状态，以不同的速度发展并具有危及生命的后果。沿着脓毒症时间线对患者进行分期需要全面了解组织水平的细胞和分子事件的演变。在这里，我们研究了肾脏，它是脓毒症病理生理学的核心器官。小鼠内毒素血症模型中的单细胞 RNA 测序揭示了各种细胞群的参与在时间上是有组织的和高度协调的。内皮细胞和基质细胞是第一反应者。在稍后的时间点，上皮细胞上调免疫相关通路，同时下调生理功能，如溶质稳态。内毒素后 16 小时，出现了全球细胞-细胞通讯失败和器官关闭。尽管有这种明显的器官麻痹，上游监管分析显示参与愈合和恢复的途径有显着活性。这种对鼠内毒素血症的严格时空定义将揭示有助于分期和治疗人类败血症的精确生物标志物和靶标。