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| Status |
Public on Nov 21, 2017 |
| Title |
Elevated p53 Activaties Restrict Differentiation Potential of microRNA-deficient Pluripotent Stem Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Pluripotent stem cells (PSCs) deficient for microRNAs (miRNAs), such as Dgcr8-/- or Dicer-/- embryonic stem cells (ESCs), contain no mature miRNA and cannot differentiate into somatic cells. How miRNA deficiency causes differentiation defects remains poorly understood. Here, we report that miR-302 is sufficient to enable neural differentiation of differentiation-incompetent Dgcr8-/- ESCs. Our data showed that miR-302 directly suppresses the tumor suppressor p53, which is modestly upregulated in Dgcr8-/- ESCs and serves as a barrier restricting neural differentiation. We demonstrated that direct inactivation of p53 by SV40 large T antigen, a short hairpin RNA against Trp53, or genetic ablation of Trp53 in Dgcr8-/- PSCs enables neural differentiation, while activation of p53 by the MDM2 inhibitor nutlin-3a in wild-type ESCs inhibits neural differentiation. Together, we demonstrate that a major function of miRNAs in neural differentiation is suppression of p53 and that modest activation of p53 blocks neural differentiation of miRNA-deficient PSCs.
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| Overall design |
Total RNAs extracted from three independent biological samples of Dgcr8-/--shctrl or Dgcr8-/--302 ESCs were submitted for microarray analysis
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| Contributor(s) |
Zhao R |
| Citation(s) |
29141234 |
| |
| Submission date |
Oct 03, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Hu Li |
| E-mail(s) |
li.hu@mayo.edu
|
| Organization name |
Mayo Clinic
|
| Department |
Molecular Pharmacology & Experimental Therapeutics
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| Lab |
Systems Biology and Pharmacology
|
| Street address |
200 First Street, Gonda Building G19-408
|
| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55904 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA413063 |
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