The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline.
acute kidney injury
human
immunology
inflammation
medicine
mouse
sepsis
single-cell RNA-seq
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
19
08
2020
accepted:
13
12
2020
entrez:
15
1
2021
pubmed:
16
1
2021
medline:
2
2
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33448928
doi: 10.7554/eLife.62270
pii: 62270
pmc: PMC7810465
doi:
pii:
Substances chimiques
Endotoxins
0
Banques de données
GEO
['GSE151658', 'GSE154107', 'GSE139061']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK107864
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK097512
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL091816
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079337
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK113223
Pays : United States
Organisme : NIH Office of the Director
ID : R01-DK080063
Organisme : NCATS NIH HHS
ID : UL1 TR002529
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK120524
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148282
Pays : United States
Organisme : BLRD VA
ID : I01 BX002901
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079312
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107623
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK111651
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021, Janosevic et al.
Déclaration de conflit d'intérêts
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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