{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim PG"],"funding":["NCI NIH HHS"],"pagination":["183-197.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12933725"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["33(2)"],"pubmed_abstract":["Somatic mutations in TET2 drive hyper-inflammation in clonal hematopoiesis of indeterminate potential (CHIP), but the molecular link between TET2 inactivation and myeloid immune activation remains unclear. We used in vivo genome-wide genetic perturbations enabled by ultra-diverse barcoding in primary wild-type (WT) or Tet2 knockout (KO) Cas9<sup>+</sup> hematopoietic stem-progenitor cells (HSPCs) to elucidate the basis of Tet2 KO inflammation. We uncover a metabolic circuit by which Tet2 restrains O-linked N-acetylglucosamine (O-GlcNAc) glycosyltransferase (Ogt), a Tet2 binding partner and metabolic sensor. Tet2 loss disrupts this inhibitory Tet2-Ogt interaction, and dysregulated Ogt facilitates widespread H3K4 trimethylation including lipid-related gene loci and inflammatory lipid droplet"],"journal":["Cell chemical biology"],"pubmed_title":["Metabolic control of innate immune activation in TET2-mutant clonal hematopoiesis."],"pmcid":["PMC12933725"],"funding_grant_id":["P01 CA066996","R35 CA253125"],"pubmed_authors":["Roy Burman SS","Vander Heiden MG","Miller AP","Ebert BL","Bullock K","Park P","Boileau M","Yue H","Deik A","Trinh MN","Armstrong SA","Yoon H","Clish C","Hergott CB","Pierce KA","Rutter JC","Choy AH","Ryback BA","McConkey M","Loke J","Shin W","Kim PG","Fischer ES"],"additional_accession":[]},"is_claimable":false,"name":"Metabolic control of innate immune activation in TET2-mutant clonal hematopoiesis.","description":"Somatic mutations in TET2 drive hyper-inflammation in clonal hematopoiesis of indeterminate potential (CHIP), but the molecular link between TET2 inactivation and myeloid immune activation remains unclear. We used in vivo genome-wide genetic perturbations enabled by ultra-diverse barcoding in primary wild-type (WT) or Tet2 knockout (KO) Cas9<sup>+</sup> hematopoietic stem-progenitor cells (HSPCs) to elucidate the basis of Tet2 KO inflammation. We uncover a metabolic circuit by which Tet2 restrains O-linked N-acetylglucosamine (O-GlcNAc) glycosyltransferase (Ogt), a Tet2 binding partner and metabolic sensor. Tet2 loss disrupts this inhibitory Tet2-Ogt interaction, and dysregulated Ogt facilitates widespread H3K4 trimethylation including lipid-related gene loci and inflammatory lipid droplet","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-16T20:47:46.518Z","creation":"2026-07-10T03:12:56.63Z"},"accession":"S-EPMC12933725","cross_references":{"pubmed":["41672066"],"doi":["10.1016/j.chembiol.2026.01.006"]}}