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Targeting the Mapk13-Tcf1-Slc7a5 Axis via One-Carbon Metabolic Regulation to Prevent Chronic Allograft Vasculopathy

GSE314157 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2026/04/08 Platform GPL28330
Summary
Chronic allograft vasculopathy (CAV) is driven in part by stem-like Cd4⁺ T cells, but how these cells sustain their progenitor programs during chronic rejection remains unclear. Here, a metabolic-epigenetic axis is identified in which Mapk13 phosphorylates Tcf1 at T289, enabling Tcf1 to activate the amino acid transporter Slc7a5 and enhance methionine uptake. This rewires one-carbon metabolism and increases H3k4me3 enrichment at the Tcf7 locus, thereby maintaining stem-like Cd4⁺ T cells within rejecting grafts. Disruption of this circuit-via genetic deletion of Mapk13 or Slc7a5, or through dietary methionine restriction-reduces Tcf1⁺ Cd4⁺ T cell stemness and prevents CAV in mouse models. These findings reveal the Mapk13-Tcf1-Slc7a5 axis as a critical metabolic dependency of pathogenic T cells and highlight one-carbon metabolism as a promising target to promote long-term graft survival.
Published in
Targeting the Mapk13-Tcf1-Slc7a5 Axis via One-Carbon Metabolic Regulation to Prevent Chronic Allograft Vasculopathy
Yi W, Wu D, Liu J et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026 · PMID 41538426 · doi:10.1002/advs.202520815
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Also filed as BioProject PRJNA1390187 and SRA study SRP656058. Searching any of these in the dataset finder brings you back here.

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