PUBLICATION
Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling
- Authors
- Zhu, W., Yao, X., Liang, Y., Liang, D., Song, L., Jing, N., Li, J., Wang, G.
- ID
- ZDB-PUB-150108-7
- Date
- 2015
- Source
- Development (Cambridge, England) 142(3): 465-76 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Embryonic Stem Cells/physiology*
- Neurodegenerative Diseases/therapy*
- Mediator Complex/deficiency*
- Mice
- Bone Morphogenetic Proteins/metabolism
- Cell Differentiation/genetics
- Cell Differentiation/physiology*
- In Situ Hybridization
- Blotting, Western
- Signal Transduction/physiology*
- Fluorescent Antibody Technique
- Gene Expression Profiling
- Real-Time Polymerase Chain Reaction
- Microarray Analysis
- Animals
- Cell- and Tissue-Based Therapy/methods*
- Gene Knockdown Techniques
- Chromatin Immunoprecipitation
- Neurons/cytology*
- Neurons/metabolism
- PubMed
- 25564654 Full text @ Development
Citation
Zhu, W., Yao, X., Liang, Y., Liang, D., Song, L., Jing, N., Li, J., Wang, G. (2015) Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling. Development (Cambridge, England). 142(3):465-76.
Abstract
Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping