| Experiment Id | GSE70156 | Series Id | E-GEOD-70156 |
| Name | Nuclear Transfer nTreg model reveals fate-determining TCRbeta and peripheral nTreg precursors | Experiment Type | RNA-Seq |
| Study Type | WT vs. Mutant | Source | GEO |
| Curation Date | 2024-01-11 |
| description | To study the development and function of "natural-arising" T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3+ CD4+ Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) beta-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR beta-chain was able to provide stronger TCR signals. This TCR-beta driven mechanism would thus unify former per se contradicting hypotheses of TCR-dependent and -independent nTreg development. Strikingly, peripheral FoxP3- CD4+ T cells expressing the same TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate into Th1 cells but were poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells. We performed RNA-Seq analysis to determine the transcriptional differences between monoclonal FoxP3GFP-positive and -negative CD4+ T cells from NOD.TCRab.FoxP3GFP.Rag-/- and compared it with polyclonal FoxP3GFP-positive and -negative CD4+ T cells from NOD.FoxP3GFP mice |
