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Updated: Sep 14, 2025
Generation of High Quality Chromatin Immunoprecipitation DNA Template for High-throughput Sequencing ChIP-seq
Published on: April 19, 2013
Single-cell transcriptome atlas and genome-wide Mendelian randomization reveal chemokine involvement in diverse
Yang Liu1, Tao Wang2,3, Rong Wu1
1Huzhou Key Laboratory of Chronic Kidney Disease, First Affiliated Hospital, Huzhou University, Huzhou, China.
Background:
Chemokine-driven immune dysregulation is increasingly recognized as a hallmark of T2D pathogenesis(T2D), where insulin resistance and metabolic stressors drive chronic inflammation. While chemokine cascades are hypothesized to mediate diabetic immunopathology, causal mediators remain undefined.
Methods:
We employed Mendelian Randomization (MR) of genome-wide association studies to identify causal inflammatory mediators, serological validation in streptozotocin-induced murine T2D models, and single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMC) to map immune cell heterogeneity and intercellular communication networks.
Results:
MR prioritized IFN-γ, CCL7, MIF, and CXCL9 as genetically supported T2D effectors. Murine validation confirmed CCL7 and MIF as robust circulating mediators. scRNA-seq revealed compartment-specific chemokine receptor dynamics (CCR4/5/6, CXCR3/4/5, CX3CR1), dominated by enhanced CCL5-CCR5 and CCL6-CCR2 crosstalk.
Conclusion:
This work establishes a systems-level framework for chemokine signaling in T2D immunopathogenesis, identifying nodal regulators of immune crosstalk as potential therapeutic vulnerabilities.
