SPI1-mediated autophagy of peripheral blood monocyte cells as a mechanism for sepsis based on single-cell RNA sequencing.

Abstract

Autophagy has been documented to participate in immune responses and inflammatory diseases, but the mechanistic actions of monocyte autophagy in sepsis remain largely unknown. This study intends to analyze the mechanism of autophagy of peripheral blood monocyte cells (PBMCs) in sepsis based on single-cell RNA sequencing (scRNA-seq). The scRNA-seq data of PBMC samples from sepsis patients were downloaded from the GEO database, followed by identification of cell marker genes, key pathways and key genes. The bioinformatics analysis showed that the PBMC samples of sepsis patients mainly contained 9 immune cell types, among which three types of monocytes showed significant changes in cell numbers in sepsis patients. Of note, the highest autophagy score was found in the intermediate monocytes. The Annexin signaling pathway was a key pathway for the communication between monocytes and other cells. More importantly, SPI1 was predicted as a key gene in the autophagy phenotype of intermediate monocytes, and SPI1 might suppress ANXA1 transcription. The high expression of SPI1 in sepsis was confirmed by RT-qPCR and Western blot analysis. Dual luciferase reporter gene assay verified that SPI1 could bind to the promoter region of ANXA1. Furthermore, it was found that SPI1 might affect monocyte autophagy in the mouse model of sepsis through regulation of ANXA1. In conclusion, we provide insight into the mechanism underlying the septic potential of SPI1, which enhances monocyte autophagy by inhibiting the transcription of ANXA1 in sepsis.

• Authors: Wenfeng Xie, Sainan Zou, Chengcheng Dong, Chunhua Yang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 117 Pg. 109909 (Apr 2023) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 37012859 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• proto-oncogene protein Spi-1
• ANXA1 protein, human
• Proto-Oncogene Proteins

Topics

• Animals
• Mice
• Autophagy
• Leukocytes, Mononuclear
• Monocytes
• Sepsis (metabolism)
• Sequence Analysis, RNA
• Humans
• Proto-Oncogene Proteins (metabolism)