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| Status |
Public on Nov 15, 2011 |
| Title |
A genome wide RNAi screen in mouse embryonic stem cells identifies Mp1 as a key mediator of differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Despite intense investigation of intrinsic and extrinsic factors that regulate pluripotency, the process of initial fate commitment of embryonic stem (ES) cells is still poorly understood. Here, we used a genome wide shRNA screen in mouse ES cells to identify genes that are essential for initiation of differentiation. Knockdown of the scaffolding protein Mek binding protein 1 (Mp1, also known as Lamtor3, Map2k1ip1) stimulated self-renewal of ES cells, blocked differentiation and promoted proliferation. Fibroblast growth factor 4 (FGF4) signaling is required for initial fate commitment of ES cells. Knockdown of Mp1 inhibited FGF4-induced differentiation but did not alter FGF4 driven proliferation. This uncoupling of differentiation and proliferation was also observed when oncogenic Ras isoforms were over expressed in ES cells. Knockdown of Mp1 redirected FGF4 signaling from differentiation towards pluripotency and upregulated the pluripotency-related genes Esrrb, Rex1, Tcl1 and Sox2.
We also found that human germ cell tumors express low amounts of Mp1 in the invasive embryonic carcinoma and seminoma histologies and higher amounts of Mp1 in the non-invasive carcinoma in situ precursor and differentiated components. Knockdown of Mp1 in invasive germ cell tumor cells resulted in resistance to differentiation, thereby showing a functional role for Mp1 both in normal differentiation of ES cells as well as in germ cell cancer.
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| Overall design |
8 samples were analyzed, representing four different experimental conditions of which each condition was analyzed by two different shRNAs to prevent off target artifacts.
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| Contributor(s) |
Westerman BA, van Lohuizen M |
| Citation(s) |
22143885 |
| Submission date |
Oct 04, 2011 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Bart A. Westerman |
| E-mail(s) |
a.westerman@amsterdamumc.nl
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| Phone |
0031(0)20 44 49073
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| Organization name |
Cancer Center Amsterdam CCA
|
| Department |
CCA-Neurosurgery
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| Lab |
Neuro-oncology Research Group
|
| Street address |
De Boelelaan 1117
|
| City |
Amsterdam |
| ZIP/Postal code |
1081 HZ |
| Country |
Netherlands |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA147071 |
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