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| Status |
Public on Jan 23, 2018 |
| Title |
Id proteins suppress E2A-driven iNKT cell development prior to TCR selection [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Id proteins have been shown to promote the differentiation of conventional αβ and γδT cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like γδNKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Lack of Id proteins also promotes a biased TCR rearrangement in favor of iNKT cell fate prior to selection at the CD4+CD8+ double positive (DP) stage. Enhanced iNKT development in Id3-deficient mice lacking γδNKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and γδNKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional αβ T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells.
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| Overall design |
The RNA-Seq experiment included duplicates of WT DP, WT NKT, WT gamma delta, L-DKO DP, L-DKO NKT and Id3KO gamma delta T cells (where L-DKO refers to mice deficient in both Id2/Id3 and Id3KO to mice that lack Id3). Each replicate consisted of pooled cells from 2-3 mice. One WT NKT was removed from analysis due to low quality of sequencing.
The mouse strains for these experiments were either C57BL/6, or C57BL/6 and 129 hybrids.
|
| Web link |
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00042/full
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| Contributor(s) |
Roy S, J. Moore A, Love C, Reddy A, Rajagopalan D, Dave S, Li L, Murre C, Zhuang Y |
| Citation(s) |
29416542 |
| |
| Submission date |
Nov 15, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Yuan Zhuang |
| E-mail(s) |
yuan.zhuang@duke.edu
|
| Phone |
919-613-7824
|
| Organization name |
Duke University
|
| Department |
Immunology
|
| Lab |
Zhuang lab
|
| Street address |
207 Research Drive
|
| City |
Durham |
| State/province |
NC |
| ZIP/Postal code |
27705 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE89849 |
Id proteins suppress E2A-driven iNKT cell development prior to TCR selection |
|
| Relations |
| BioProject |
PRJNA354280 |
| SRA |
SRP096043 |
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