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| Status |
Public on Apr 04, 2016 |
| Title |
Nuclear Transfer nTreg model reveals fate-determining TCRbeta and peripheral nTreg precursors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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) β-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 β-chain was able to provide stronger TCR signals. This TCR-β–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.
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| Overall design |
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
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| Contributor(s) |
Kirak O, Ku M, Ke E |
| Citation(s) |
27044095 |
| Submission date |
Jun 23, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Manching Ku |
| Organization name |
Medical Center - University of Freiburg
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| Department |
Hematology and Oncology
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| Street address |
Mathildenstrasse 1
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| City |
Freiburg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA287758 |
| SRA |
SRP059777 |
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