|
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.
|
|
|
Overall design |
Gene expressions comparing cells cultured on different stiffnesses
|
|
|
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 |
|
|
Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
Samples (4)
|
|
This SubSeries is part of SuperSeries: |
|
Relations |
BioProject |
PRJNA416280 |
SRA |
SRP122908 |