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Series GSE267242 Query DataSets for GSE267242
Status Public on May 23, 2024
Title Single-cell sequencing reveals Mincle receptor mediated inflammation for resolution in ischemic kidney injury
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Recent studies have demonstrated a strong association between acute kidney injury (AKI) and chronic kidney disease (CKD), while the unresolved inflammation is believed to be a driving force for this chronic transition process. As a transmembrane pattern recognition receptor, Mincle (macrophage-inducible C-type lectin, Clec4e) was identified to participate in the early immune response after AKI. However, the impact of Mincle on the chronic transition of AKI remains largely unclear. We performed single-cell RNA sequencing (scRNA-seq) with the unilateral ischemia-reperfusion (UIR) murine model of AKI at days 1, 3, 14 and 28 after injury. Potential effects and mechanism of Mincle on renal inflammation and fibrosis were further validated in vivo utilizing Mincle knockout mice. The dynamic expression of Mincle in macrophages and neutrophils throughout the transition from AKI to CKD was observed. For both cell types, Mincle expression was significantly up-regulated on day 1 following AKI, with a second rise observed on day 14. Notably, we identified distinct subclusters of Mincle-high neutrophils and Mincle-high macrophages that exhibited time-dependent influx with dual peaks characterized with remarkable pro-inflammatory and pro-fibrotic functions. Moreover, we identified that Mincle-high neutrophils represented an "aged" mature neutrophil subset derived from the "young" mature neutrophil cluster in kidney. Additionally, we observed a synergistic mechanism whereby Mincle-expressing macrophages and neutrophils sustained renal inflammation by augmenting tumor necrosis factor (TNF) production. Mincle-deficient mice exhibited reduced renal injury and fibrosis following AKI.
Overall design Unilateral ischemia-reperfusion (UIR) murine model of AKI at days 1, 3, 14 and 28.
Citation(s) 38770013
Submission date May 12, 2024
Last update date May 23, 2024
Contact name Ning Li
Organization name Southeast University
Street address Nanjing
City Nanjing
ZIP/Postal code 210029
Country China
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (5)
GSM8262827 AKI day 1
GSM8262828 AKI day 3
GSM8262829 AKI day 14
BioProject PRJNA1110735

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Supplementary file Size Download File type/resource
GSE267242_barcodes.tsv.gz 33.5 Mb (ftp)(http) TSV
GSE267242_features.tsv.gz 284.1 Kb (ftp)(http) TSV
GSE267242_matrix.mtx.gz 717.6 Mb (ftp)(http) MTX
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