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The TET2 methylcytosine dioxygenase regulates early and late transitions in exhausted CD8+ T-cell differentiation

GSE261093 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 51 samples Submitted 2025/04/14 Platform GPL21626Platform GPL24676
Summary
Epigenetic reprogramming of CAR T-cells by targeting TET2, a methylcytosine deoxygenase that mediates active DNA demethylation, has shown therapeutic potential; however, the role of TET2 in TEX development is unclear. In both CAR T-cell exhaustion models in vitro and chronic LCMV infection in vivo, TET2 drove the conversion from memory-like, self-renewing TEX progenitors towards effector (TEFF)-like and terminally differentiated TEX. TET2-deficient terminally differentiated TEX retained aspects of TEX progenitor biology, including decreased expression of the transcription factor TOX, suggesting that TET2 is required for terminal exhaustion.
Published in
TET2 regulates early and late transitions in exhausted CD8(+) T cell differentiation and limits CAR T cell function
Dimitri AJ, Baxter AE, Chen GM et al. · Science advances 2024 · PMID 39536093 · doi:10.1126/sciadv.adp9371
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Also filed as BioProject PRJNA1085279 and SRA study SRP493938. Searching any of these in the dataset finder brings you back here.

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