{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE224402"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Epigenetic control of T cells by vitamin C via DNA demethylation [RNAseq in vitro stimulation] ","description":"Maintenance of T cell naïve (Tn) state and restricting effector T cell differentiation upon basal level stimulations would be critical for immune homeostasis and prevention of autoimmunity. To understand how Tn state is regulated by nutrient cues in a cell-intrinsic manner, here we perform an in vivo CRISPR screening to identify required solute carrier (SLC) proteins that transport metabolites and ions into T cells. Among SLC proteins revealed by this experiment, vitamin C transporter Slc23a2 appears to play a role. Conditional ablation of Slc23a2 in T cells by genetic approaches reduces intracellular vitamin C levels by approximately 80%, accompanied by spontaneous activation and differentiation of Tn cells, autoantibody production, and autoimmune pathology in select organs. Slc23a2-deficient Tn cells exhibit profound DNA hypermethylation, dysregulation of genes controlling signaling transduction and transcription, and enhanced differentiation of helper T cells upon stimulation. These results define a broad regulatory space of vitamin C as a cofactor of Tet enzymes in controlling active DNA demethylation. In agreement, conditional deletion of Tet genes impairs Tn state and increases helper T cell differentiation. Thus, our study reveals a cell-intrinsic mechanism by which micronutrient vitamin C via Slc23a2 maintains Tn state and self-tolerance by promoting Tet-mediated DNA demethylation.","dates":{"publication":"2026/05/08"},"accession":"GSE224402","cross_references":{"GSM":["GSM7021756","GSM7021745","GSM7021744","GSM7021755","GSM7021754","GSM7021753","GSM7021752","GSM7021751","GSM7021761","GSM7021750","GSM7021760","GSM7021749","GSM7021748","GSM7021759","GSM7021758","GSM7021747","GSM7021746","GSM7021757"],"GPL":["24247"],"GSE":["224402"],"taxon":["Mus musculus"]}}