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| Status |
Public on Feb 14, 2018 |
| Title |
B cell development requires discrete regulation by PTEN-PI3K and mTOR pathways and the intricate interplay with IL-7 r-Stat5 signaling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
IL-7 r and Stat5 signaling drives early B lymphopoiesis, but it remains poorly understood how Stat5-dependent and independent pathways contribute to this process. We report the discrete effects of PI3K and mTOR signaling on Stat5 signaling and B cell development. PI3K was not engaged by IL-7 in pro-B cells but was actively suppressed by PTEN to ensure proper IL-7 r expression, Stat5 signaling and pro-B cell survival. Further, IL-7-mediated mTORC1 activation, which was uncoupled from PI3K signaling, orchestrated a unique program in early B cell development in a Stat5-independent but Myc-dependent manner. mTORC1 was also required for immunoglobulin heavy chain rearrangement and Myc-driven lymphomagenesis. Finally, mTORC2 was not essential for early B cell development but contributed to peripheral B cell maturation. Altogether, genetic dissection of PI3K, mTORC1, and mTORC2 reveals the distinct effects of these seemingly related pathways on B cell development and the intricate interplay between PI3K, mTOR and IL-7 r-Stat5 signaling.
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| Overall design |
We used microarrays to explore the gene expression profiles differentially expressed in untreated and IL-7 treated B220+CD43+IgM- pro-B cells from Cre^(ER)/Rptor^(fl/+) and Cre^(ER)/Rptor^(fl/fl) mice 7 days after tamoxifen treatment.
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| |
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| Contributor(s) |
Zeng H, Neale G, Chi H |
| Citation(s) |
29399633 |
| |
| Submission date |
May 24, 2016 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
|
| Organization name |
St Jude Childrens Research Hospital
|
| Department |
Hartwell Center
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (12)
|
| GSM2176548 |
Cre^(ER)/Rptor^(fl/+) pro-B cells untreated replicate 1 |
| GSM2176549 |
Cre^(ER)/Rptor^(fl/+) pro-B cells untreated replicate 2 |
| GSM2176550 |
Cre^(ER)/Rptor^(fl/+) pro-B cells untreated replicate 3 |
| GSM2176551 |
Cre^(ER)/Rptor^(fl/fl) pro-B cells untreated replicate 1 |
| GSM2176552 |
Cre^(ER)/Rptor^(fl/fl) pro-B cells untreated replicate 2 |
| GSM2176553 |
Cre^(ER)/Rptor^(fl/fl) pro-B cells untreated replicate 3 |
| GSM2176554 |
Cre^(ER)/Rptor^(fl/+) pro-B cells treated with IL-7 replicate 1 |
| GSM2176555 |
Cre^(ER)/Rptor^(fl/+) pro-B cells treated with IL-7 replicate 2 |
| GSM2176556 |
Cre^(ER)/Rptor^(fl/+) pro-B cells treated with IL-7 replicate 3 |
| GSM2176557 |
Cre^(ER)/Rptor^(fl/fl) pro-B cells treated with IL-7 replicate 1 |
| GSM2176558 |
Cre^(ER)/Rptor^(fl/fl) pro-B cells treated with IL-7 replicate 2 |
| GSM2176559 |
Cre^(ER)/Rptor^(fl/fl) pro-B cells treated with IL-7 replicate 3 |
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| Relations |
| BioProject |
PRJNA322694 |
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