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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 03, 2011 |
| Title |
Identification of Tfeb-dependent genes downstream of mTORC1 in MEFs |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a critical regulator of cell growth by integrating multiple signals (nutrients, growth factors, energy and stress) and is frequently deregulated in many types of cancer. We used a robust experimental paradigm involving the combination of two interventions, one genetic and one pharmacologic to identify genes regulated transcriptionally by mTORC1. In Tsc2+/+, but not Tsc2-/- immortalized mouse embryo fibroblasts (MEFs), serum deprivation downregulates mTORC1 activity. In Tsc2-/- cells, abnormal mTORC1 activity can be downregulated by treatment with rapamycin (sirolimus). By contrast, rapamycin has little effect on mTORC1 in Tsc2+/+ cells in which mTORC1 is already inhibited by low serum. Thus, under serum deprived conditions, mTORC1 activity is low in Tsc2+/+ cells (untreated or rapamycin treated), high in Tsc2-/- cells, but lowered by rapamycin; a pattern referred to as a “low/low/high/low” or “LLHL”. We found that mTORC1 regulated the expression of, among other lysosomal genes, V-ATPases through the transcription factor EB (TFEB, Tcfeb in the mouse). The knockdown of Tfeb resulted in the 'flattening' of the LLHL pattern and allowed the identification of genes regulated by mTORC1 through Tfeb
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| Overall design |
Mouse embryo fibroblasts (MEFs) wild type or deficient in Tsc2 expressing a Tfeb shRNA or scrambled shRNA vector were treated with 25 nM rapamycin or vehicle (methanol) for 24 h under low serum conditions (0.1% FBS)
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| Contributor(s) |
Peña-Llopis S, Brugarolas J |
| Citation(s) |
21804531 |
| Submission date |
Mar 17, 2011 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Samuel Peña-Llopis |
| E-mail(s) |
Samuel.Pena-Llopis@UTSouthwestern.edu, James.Brugarolas@UTSouthwestern.edu
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| Phone |
(01) 214-648-4099
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| Fax |
(01) 214-648-1960
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| Organization name |
UT Southwestern Medical Center
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| Department |
Internal Medicine - Oncology Division
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| Lab |
Brugarolas Lab
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| Street address |
6000 Harry Hines Blvd., NB5.102
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9133 |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (18)
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| GSM692907 |
wt MEFs, scrambled shRNA, vehicle, rep1 |
| GSM692908 |
wt MEFs, scrambled shRNA, vehicle, rep2 |
| GSM692909 |
wt MEFs, scrambled shRNA, rapamycin, rep1 |
| GSM692910 |
wt MEFs, scrambled shRNA, rapamycin, rep2 |
| GSM692911 |
Tsc2-/- MEFs, scrambled shRNA, vehicle, rep1 |
| GSM692912 |
Tsc2-/- MEFs, scrambled shRNA, vehicle, rep2 |
| GSM692913 |
Tsc2-/- MEFs, scrambled shRNA, vehicle, rep3 |
| GSM692914 |
Tsc2-/- MEFs, scrambled shRNA, rapamycin, rep1 |
| GSM692915 |
Tsc2-/- MEFs, scrambled shRNA, rapamycin, rep2 |
| GSM692916 |
wt MEFs, Tfeb shRNA, vehicle, rep1 |
| GSM692917 |
wt MEFs, Tfeb shRNA, vehicle, rep2 |
| GSM692918 |
wt MEFs, Tfeb shRNA, rapamycin, rep1 |
| GSM692919 |
wt MEFs, Tfeb shRNA, rapamycin, rep2 |
| GSM692920 |
Tsc2-/- MEFs, Tfeb shRNA, vehicle, rep1 |
| GSM692921 |
Tsc2-/- MEFs, Tfeb shRNA, vehicle, rep2 |
| GSM692922 |
Tsc2-/- MEFs, Tfeb shRNA, vehicle, rep3 |
| GSM692923 |
Tsc2-/- MEFs, Tfeb shRNA, rapamycin, rep1 |
| GSM692924 |
Tsc2-/- MEFs, Tfeb shRNA, rapamycin, rep2 |
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| Relations |
| BioProject |
PRJNA137965 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28021_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE28021_non-normalized.txt.gz |
5.1 Mb |
(ftp)(http) |
TXT |
| GSE28021_normalized.txt.gz |
5.1 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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