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| Status |
Public on Jan 15, 2009 |
| Title |
PPAR Controls Gene Expression in MSC Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Rosiglitazone (Rosi), a member of the thiazolidinedione class of drugs used to treat type 2 diabetes, activates the adipocyte-specific transcription factor peroxisome proliferator-activated receptor gamma (PPARg). This activation causes bone loss in animals and humans, at least in part due to suppression of osteoblast differentiation from marrow mesenchymal stem cells (MSC). In order to identify mechanisms by which PPARg2 suppresses osteoblastogenesis and promotes adipogenesis in MSC, we have analyzed the PPARg2 transcriptome in response to Rosi. A total of 4,252 transcriptional changes resulted when Rosi (1 uM) was applied to the U-33 marrow stromal cell line, stably transfected with PPARg2 (U-33/g2), as compared to non-induced U-33/g2 cells. Differences between U-33/g2 and U-33 cells stably transfected with empty vector (U-33/c) comprised 7,928 transcriptional changes, independent of Rosi. Cell type-, time- and treatment-specific gene clustering uncovered distinct patterns of PPARg2 transcriptional control of MSC lineage commitment. The earliest changes accompanying Rosi activation of PPARg2 included adjustments in morphogenesis, Wnt signaling, and immune responses, as well as sustained induction of lipid metabolism. Expression signatures influenced by longer exposure to Rosi provided evidence for distinct mechanisms governing the repression of osteogenesis and stimulation of adipogenesis. Our results suggest interactions that could lead to the identification of a “master” regulatory scheme controlling osteoblast differentiation.
Keywords: rosiglitazone, PPARgamma, microarray, time course, gene expression, stem cells
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| Overall design |
U-33/g2 and U-33/c cells were cultured in the presence or absence of Rosi and gene expression was monitored at three different time points (2, 24, 72h) after exposure to the agonist. Each time point corresponds to a separate stage of Rosi-treated U-33/g2 cell conversion from the osteoblast-like phenotype to the adipocyte-like phenotype and includes induction (2h), intermediate alterations in phenotype progression (24h), and a terminally differentiated adipocytic with completely suppressed osteoblastic phenotype (72h). The experiment is a full factorial design performed in replicate.
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| Contributor(s) |
Shockley KR, Lazarenko OP, Czernik PJ, Rosen CJ, Churchill GA, Lecka-Czernik B |
| Citation(s) |
19115254, 32995694 |
| Submission date |
Jan 16, 2008 |
| Last update date |
Oct 06, 2020 |
| Contact name |
Keith Shockley |
| Organization name |
The Jackson Laboratory
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| Department |
Computational and Systems Biology
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| Street address |
600 Main Street
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| City |
Bar Harbor |
| State/province |
ME |
| ZIP/Postal code |
04609 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (24)
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| GSM257412 |
Empty vector control, 24 hrs, Rosiglitazone (ROS_24_1) |
| GSM257414 |
Empty vector control, 24 hrs, No Rosiglitazone (NONE_24_1) |
| GSM257415 |
Empty vector control, 24 hrs, Rosiglitazone (ROS_24_2) |
| GSM257416 |
Empty vector control, 24 hrs, No Rosiglitazone (NONE_24_2) |
| GSM257417 |
Empty vector control, 72 hrs, Rosiglitazone (ROS_72_1) |
| GSM257418 |
Empty vector control, 72 hrs, No Rosiglitazone (NONE_72_1) |
| GSM257419 |
Empty vector control, 72 hrs, No Rosiglitazone (NONE_72_2) |
| GSM257420 |
PPARg2 expression construct, 2 hrs, Rosiglitazone (ACT_2_1) |
| GSM257421 |
PPARg2 expression construct, 2 hrs, No Rosiglitazone (PPAR_2_1) |
| GSM257422 |
Empty vector control, 2 hrs, Rosiglitazone (ROS_2_1) |
| GSM257423 |
Empty vector control, 2 hrs, No Rosiglitazone (NONE_2_1) |
| GSM257424 |
PPARg2 expression construct, 2 hrs, Rosiglitazone (ACT_2_2) |
| GSM257425 |
PPARg2 expression construct, 2 hrs, No Rosiglitazone (PPAR_2_2) |
| GSM257426 |
Empty vector control, 2 hrs, Rosiglitazone (ROS_2_2) |
| GSM257427 |
Empty vector control, 2 hrs, No Rosiglitazone (NONE_2_2) |
| GSM257451 |
PPARg2 expression construct, 24 hrs, Rosiglitazone (ACT_24_1) |
| GSM257452 |
PPARg2 expression construct, 24 hrs, No Rosiglitazone (PPAR_24_1) |
| GSM257453 |
PPARg2 expression construct, 24 hrs, Rosiglitazone (ACT_24_2) |
| GSM257454 |
PPARg2 expression construct, 24 hrs, No Rosiglitazone (PPAR_24_2) |
| GSM257455 |
PPARg2 expression construct, 72 hrs, Rosiglitazone (ACT_72_1) |
| GSM257456 |
PPARg2 expression construct, 72 hrs, No Rosiglitazone (PPAR_72_1) |
| GSM257457 |
PPARg2 expression construct, 72 hrs, Rosiglitazone (ACT_72_2) |
| GSM257458 |
PPARg2 expression construct, 72 hrs, No Rosiglitazone (PPAR_72_2) |
| GSM257463 |
Empty vector control, 72 hrs, Rosiglitazone (ROS_72_2) |
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| Relations |
| BioProject |
PRJNA108303 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10192_RAW.tar |
81.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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