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| Status |
Public on Apr 18, 2018 |
| Title |
Srf destabilizes cell identity (RNA-seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Multicellular organisms consist of multiple cell types, whose identities are maintained appropriately at locations where they are reside. The identity of each cell type is primarily maintained by cell-type-specific gene expression programs, but mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease β-actin monomer resulted in nuclear accumulation of Mkl1 and the activation of Srf, which downregulated cell-type-specific genes and altered epigenetics in enhancers and chromatin organization. Mice overexpressing Srf exhibited various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.
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| Overall design |
Gene expressions comparing cells cultured on different stiffnesses
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| |
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| Contributor(s) |
Ikeda T, Hikichi T, Yamamoto T, Okita K, Masui S |
| Citation(s) |
29643333 |
| |
| Submission date |
Oct 30, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Takashi Ikeda |
| E-mail(s) |
tikeda@cira.kyoto-u.ac.jp
|
| Organization name |
Kyoto Univ.
|
| Street address |
53 Shogoin Kawahara-cho Sakyo-ku
|
| City |
Kyoto |
| ZIP/Postal code |
6068507 |
| Country |
Japan |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA416280 |
| SRA |
SRP122908 |
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