GEO series
Metabolic control of innate immune activation in TET2-mutant clonal hematopoiesis [ChIP-seq]
GSE309775
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
44 samples
Submitted 2026/01/15
Platform GPL19057Platform GPL18573
Summary
TET2 mutations drive inflammation in clonal hematopoiesis of indeterminate potential (CHIP), but the mechanism by which TET2 inactivation leads to inflammation is not understood. Here, we used in vivo genome-wide genetic perturbations in primary wildtype (WT) or Tet2 knockout (KO) Cas9+ hematopoietic stem-progenitor cells (HSPCs) in a model of zymosan peritonitis to elucidate the basis of Tet2 KO inflammation. We found that Tet2 restrains O-linked N-acetylglucosamine (O-GlcNAc) glycosyltransferase (Ogt), a Tet2 binding partner and metabolic sensor that integrates nutrient availability. Tet2 loss disrupts this Tet2-Ogt interaction, and dysregulated Ogt facilitates widespread H3K4 trimethylation including lipid-related gene loci and inflammatory lipid droplet formation. We identified ATP citrate lyase (Acly) as a critical node for lipid accumulation, inflammation, and myeloid expansion in Tet2 deficiency. In summary, we reveal that Tet2 serves as a negative regulator of the nutrient sensor Ogt, and that Tet2 inactivation leads to aberrant lipid droplet formation and inflammation.
Published in
Kim PG, Hergott CB, Miller AP et al.
· Cell chemical biology 2026
· PMID 41672066
· doi:10.1016/j.chembiol.2026.01.006
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE309775_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 44 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1363152 and SRA study SRP644306. Searching any of these in the dataset finder brings you back here.
Study design
38 conditions, each sampled once — no replicated groups
Tet2 KO BMDMs treated with glucose, 55mM, 24 … ×2
WT BMDMs treated with glucose, 55mM, 24 hrs; … ×2
Supports a case/control comparison: 9 samples read as cases, 12 as controls.
Read from the first 40 of 44 sample titles: 38 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9278838 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 0.1ng/ml, IP: H3K4me3
- GSM9278839 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 1ng/ml, IP: H3K4me3
- GSM9278840 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 100ng/ml, IP: H3K4me3
- GSM9278841 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 0.1ng/ml, IP: H3K4me3
- GSM9278842 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 1ng/ml, IP: H3K4me3
- GSM9278843 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 100ng/ml, IP: H3K4me3
- GSM9278844 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 0.1ng/ml, IP: H3K27ac
- GSM9278845 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 1ng/ml, IP: H3K27ac
- GSM9278846 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 100ng/ml, IP: H3K27ac
- GSM9278847 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 0.1ng/ml, IP: H3K27ac
- GSM9278848 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 1ng/ml, IP: H3K27ac
- GSM9278849 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 100ng/ml, IP: H3K27ac
- GSM9278850 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 0.1ng/ml, IP: Strepavidin
- GSM9278851 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 1ng/ml, IP: Strepavidin
- GSM9278852 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 100ng/ml, IP: Strepavidin
- GSM9278853 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 0.1ng/ml, IP: Strepavidin
- GSM9278854 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 1ng/ml, IP: Strepavidin
- GSM9278855 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 100ng/ml, IP: Strepavidin
- GSM9278856 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 0.1ng/ml, input
- GSM9278857 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 1ng/ml, input
- GSM9278858 WT U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 100ng/ml, input
- GSM9278859 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 0.1ng/ml, input
- GSM9278860 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 1ng/ml, input
- GSM9278861 TET2KO U937 cells expressing doxycycline-inducible TurboID OGT, 18hr induction dox 100ng/ml, input
- GSM9278862 Tet2 KO BMDMs treated with galactose, 55mM, 24 hrs; IP: Ogt
- GSM9278863 Tet2 KO BMDMs treated with glucose, 12mM, 24 hrs; IP: GlcNAc
- GSM9278864 Tet2 KO BMDMs treated with glucose, 12mM, 24 hrs; IP: Ogt
- GSM9278865 Tet2 KO BMDMs treated with sucrose, 55mM, 24 hrs; IP: Ogt
- GSM9278866 Tet2 KO BMDMs treated with glucose, 55mM, 24 hrs; IP: GlcNAc
- GSM9278867 Tet2 KO BMDMs treated with glucose, 55mM, 24 hrs; IP: H3K4me1
- GSM9278868 Tet2 KO BMDMs treated with glucose, 55mM, 24 hrs; IP: H3K4me3
- GSM9278869 Tet2 KO BMDMs treated with glucose, 55mM, 24 hrs; IP: H3K27me3
- GSM9278870 Tet2 KO BMDMs treated with glucose, 55mM, 24 hrs; IP: Ogt
- GSM9278871 Tet2 KO BMDMs input
- GSM9278872 WT BMDMs treated with galactose, 55mM, 24 hrs; IP: Ogt
- GSM9278873 WT BMDMs treated with glucose, 12mM, 24 hrs; IP: GlcNAc
- GSM9278874 Wt BMDMs treated with glucose, 12mM, 24 hrs; IP: Ogt
- GSM9278875 WT BMDMs treated with glucose, 55mM, 24 hrs; IP: GlcNAc
- GSM9278876 WT BMDMs treated with glucose, 55mM, 24 hrs; IP: H3K4me1
- GSM9278877 WT BMDMs treated with glucose, 55mM, 24 hrs; IP: H3K4me3
+ 4 more — browse all 44 samples with per-sample file links →
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