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Janosevic D, Myslinski J, McCarthy TW, et al. The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline. Elife. 2021;10doi: 10.7554/eLife.62270.
Janosevic, D., Myslinski, J., McCarthy, T. W., Zollman, A., Syed, F., Xuei, X., Gao, H., Liu, Y. L., Collins, K. S., Cheng, Y. H., Winfree, S., El-Achkar, T. M., Maier, B., Melo Ferreira, R., Eadon, M. T., Hato, T., & Dagher, P. C. (2021). The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline. eLife, 10. https://doi.org/10.7554/eLife.62270
Janosevic, Danielle, et al. "The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline." eLife vol. 10 (2021). doi: https://doi.org/10.7554/eLife.62270
Janosevic D, Myslinski J, McCarthy TW, Zollman A, Syed F, Xuei X, Gao H, Liu YL, Collins KS, Cheng YH, Winfree S, El-Achkar TM, Maier B, Melo Ferreira R, Eadon MT, Hato T, Dagher PC. The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline. Elife. 2021 Jan 15;10. doi: 10.7554/eLife.62270. PMID: 33448928; PMCID: PMC7810465.
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Elife. 2021 Jan 15;10. doi: 10.7554/eLife.62270.

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

eLife

Danielle Janosevic, Jered Myslinski, Thomas W McCarthy, Amy Zollman, Farooq Syed, Xiaoling Xuei, Hongyu Gao, Yun-Long Liu, Kimberly S Collins, Ying-Hua Cheng, Seth Winfree, Tarek M El-Achkar, Bernhard Maier, Ricardo Melo Ferreira, Michael T Eadon, Takashi Hato, Pierre C Dagher

Affiliations

  1. Department of Medicine, Indiana University School of Medicine, Indianapolis, United States.
  2. Department of Pediatrics and the Herman B. Wells Center, Indiana University School of Medicine, Indianapolis, United States.
  3. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, United States.
  4. Roudebush Indianapolis Veterans Affairs Medical Center, Indianapolis, United States.

PMID: 33448928 PMCID: PMC7810465 DOI: 10.7554/eLife.62270

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.

© 2021, Janosevic et al.

Keywords: acute kidney injury; human; immunology; inflammation; medicine; mouse; sepsis; single-cell RNA-seq

Conflict of interest statement

DJ, JM, TM, AZ, FS, XX, HG, YL, KC, YC, SW, TE, BM, RM, ME, TH, PD No competing interests declared

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