|
| Status |
Public on Jan 20, 2019 |
| Title |
Suppression of ILC2 differentiation from committed T cell precursors by E protein transcription factors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Current models propose that group 2 innate lymphoid cells are generated in the bone marrow. Here we demonstrate that subsets of these cells can differentiate from multipotent progenitors and committed T cell precursors in the thymus, both in vivo and in vitro. These thymic ILC2s can exit the thymus, circulate in the blood and home to peripheral tissues. Ablation of E protein transcription factors greatly promotes the innate lymphoid cell fate at the expense of B and T cell development. Consistently, a transcriptional network centered on the ZBTB16 transcription factor and IL-4 signaling pathway is highly up-regulated due to E protein deficiency. Our results show that ILC2 can still be generated from what are normally considered to be committed T cell precursors, and that this alternative cell fate is restrained by high levels of E protein activity in these cells.
|
| |
|
| Overall design |
RNA-seq was performed on freshly isolated ILC2 cells from the thymus, mesenteric lymph nodes and lung of different strains of mice. Cells cultured from DN1 or DN3 thymocytes on OP9-DL1 stromal cells in the presence IL-2, IL-7 and Stem cell factor were also analyzed. The genotypes of the mice where DN1 and DN3 cells were obtained are ROSA26-CreERT2;ROSA26-stop-tdTomato and ROSA26-CreERT2;ROSA26-stop-tdTomato;E2Af/f/HEBf/f. Addition of tamoxifen on Day 4 to the cultures induces deletion of the HEB and E2A gene as well as the expression of tdTomato. On Day 5 and Day7 of the culture, tdTomato positive cells were sorted and used for RNA isolation.
|
| |
|
| Contributor(s) |
Sun X, Georgescu C, Adrianto I |
| Citation(s) |
30898894 |
| |
| Submission date |
Mar 07, 2018 |
| Last update date |
Apr 22, 2019 |
| Contact name |
Jonathan Wren |
| E-mail(s) |
Jonathan-Wren@omrf.org
|
| Phone |
(405) 271-6989
|
| Organization name |
OMRF
|
| Department |
Genes & Human Disease Research Program
|
| Street address |
825 N.E. 13th Street
|
| City |
Oklahoma City |
| State/province |
OK |
| ZIP/Postal code |
73104 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (31)
|
|
| Relations |
| BioProject |
PRJNA437289 |
| SRA |
SRP134096 |
Less...
More...