Description: The liver macrophage population comprises resident Kupffer cells (KCs) and monocyte-derived macrophages, with distinct pro- or anti-inflammatory properties that affect the severity and course of liver diseases. The mechanisms underlying macrophage differentiation and function in metabolic dysfunction-associated steatotic liver disease and/or steatohepatitis (MASLD/MASH) remain mostly unknown. Using single-cell RNA sequencing and fate mapping of hepatic macrophage subpopulations, we unraveled the temporal and spatial dynamics of distinct monocyte and monocyte-derived macrophage subsets in MASH. We revealed a crucial role for the Notch-RBPJ signaling pathway in controlling the monocyte-to-macrophage transition, with Rbpj deficiency blunting inflammatory macrophages and monocyte-derived KCs differentiation and conversely promoting the emergence of protective Ly6Clo monocytes. Mechanistically, Rbpj-deficiency promoted lipid uptake driven by elevated CD36 expression in Ly6Clo monocytes, enhancing their protective interactions with endothelial cells. Our findings uncover the crucial role of Notch-RBPJ signaling in monocyte-to-macrophage transition and will aid the design of therapeutic strategies for MASH treatment.

Data type: Transcriptome or Gene expression

Sample scope: Monoisolate

Release date: 2024-09-23

Last updated: 2024-10-08

Data size: 328.14GB