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Temporal Transcriptomic Profiling of MutuDC Cells Treated with Fanchinoline Reveals Mechanistic Insights

ABSTRACT: This study investigates the mechanistic effects of Fanchinoline on Murine dendritic cell line MutuDC by performing temporal transcriptomic analysis. We treated MutuDC cells with Fanchinoline and collected samples at 0, 2, 6, 12, and 24 hours post-treatment to examine the dynamic changes in gene expression. Our data provides comprehensive insights into the regulatory pathways and biological processes influenced by Fanchinoline, highlighting its potential impact on immune response modulation and cellular function in dendritic cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE271465 | GEO | 2026/07/01

REPOSITORIES: GEO

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Project description:Systematic analyses of the temporal dynamics of transcriptomes and chromatin landscapes of macrophages during timecourse of TLR4-mediated inflammatory response. As a multifunctional effector cell, macrophages play pivotal roles in both the induction and resolution components of varied inflammatory processes. During the course of an inflammation response, macrophages engage in a homeostatic program characterized by tightly coordinated modulation of temporal outputs of both lipid metabolism and inflammation. We demonstrate inversely biphasic temporal dynamics of specific fatty acid metabolic and inflammatory gene expression profiles, associated with concordant temporal reprogramming of macrophage fatty acid profiles. In part, the late phase of the macrophage inflammatory response is characterized by tailoring of fatty acid related gene expressions, facilitating both significant induction of anti-inflammatory unsaturated fatty acid production and associated resolution of inflammation. We demonstrate the biphasic temporal dynamics of macrophage inflammation, specifically anti-inflammatory omega-3 and omega-9 unsaturated fatty acid levels, are transcriptionally driven genome-wide by an unexpected shift from an LXR to SREBP1-dominant regulatory program in the late phase inflammatory response. Collectively, our findings reveal a novel Srebp1-driven mechanism allowing the intimate inverse temporal relationship between the transcriptional regulation of inflammatory and fatty acid metabolic outputs; whereby modulation key transcriptional regulators (LXR, SREBP1 and NF-kB) of these pathways coordinate appropriate temporal tailoring of local enhancer associated reprogramming and eventual pathway regulatory interactions, during the course of TLR4-dependent inflammatory response in macrophages. This specific Srebp-driven, temporal reprogramming of macrophage fatty acid metabolism, characterized by late phase induction of anti-inflammatory unsaturated fatty acid production, is necessary for appropriate resolution of inflammation. Thus, this study suggests that selective reprogramming of macrophage lipid metabolism can serve as a viable therapeutic intervention aimed at ameliorating chronic inflammation and varied metabolic syndrome associated states.

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Temporal Transcriptomic Profiling of MutuDC Cells Treated with Fanchinoline Reveals Mechanistic Insights

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