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Single-Cell Multi-omics Profiling of Mouse Hepatic Immune Microenvironment Reveals Neutrophil-Kupffer Cell Crosstalk via Thrombospondin-1/CD36 after Surgical Stress

ABSTRACT: The hepatic immune microenvironment comprises both innate and adaptive immune responses, to surgical stress during liver surgeries, leading to ischemia/reperfusion (I/R) injury. Traditional approaches to treat I/R injury have predominantly targeted single, known injury mechanisms, often overlooking the complexity of the hepatic immune microenvironment. Consequently, pharmaceutical interventions focusing on isolated pathways have yielded minimal therapeutic success, underscoring an urgent need for a more comprehensive understanding of the underlying cellular and molecular dynamics. By leveraging single-cell multi-omics technologies, we dissected the multifaceted cellular interactions and molecular alterations within the hepatic immune microenvironment post-surgery. Importantly, we demonstrate that targeting the interaction between infiltrating neutrophils and hepatic resident macrophages, Kupffer cells, through the thrombospondin-1/CD36 pathway during liver I/R. Together, these findings unveil extensive reprogramming of immune cell populations and activation of multiple signaling pathways in response to surgical stress, emphasizing the significance of myeloid cell interactions. This research opens avenues for investigating interactions among different hepatic immune cell types in response to liver damage.

ORGANISM(S): Mus musculus

PROVIDER: GSE315482 | GEO | 2026/07/15

REPOSITORIES: GEO

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