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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
Acquisition of neural fate by combination of BMP blockade and chromatin modification
Agnes Lee Chen Ong1, Toshiya Kokaji2, Arisa Kishi1
1Division of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma 630-0192, Japan.
Abstract:
Neural induction is a process where naive cells are converted into committed cells with neural characteristics, and it occurs at the earliest step during embryogenesis. Although the signaling molecules and chromatin remodeling for neural induction have been identified, the mutual relationships between these molecules are yet to be fully understood. By taking advantage of the neural differentiation system of mouse embryonic stem (ES) cells, we discovered that the BMP signal regulates the expression of several polycomb repressor complex (PRC) component genes. We particularly focused on Polyhomeotic Homolog 1 (Phc1) and established Phc1-knockout (Phc1-KO) ES cells. We found that Phc1-KO failed to acquire the neural fate, and the cells remained in pluripotent or primitive non-neural states. Chromatin accessibility analysis suggests that Phc1 is essential for chromatin packing. Aberrant upregulation of the BMP signal was confirmed in the Phc1 homozygotic mutant embryos. Taken together, Phc1 is required for neural differentiation through epigenetic modification.
Insights
Polyhomeotic Homolog 1 (Phc1) is crucial for neural differentiation. Its absence prevents neural fate acquisition by affecting chromatin packing and BMP signaling, highlighting its role in epigenetic modification during early development.
Area of Science:
- Developmental Biology
- Epigenetics
- Stem Cell Biology
Background:
- Neural induction is a fundamental early embryogenesis process.
- The interplay between signaling molecules and chromatin remodeling in neural induction requires further elucidation.
- Mouse embryonic stem cells provide a valuable model for studying neural differentiation.
Purpose of the Study:
- To investigate the role of Polycomb Repressor Complex (PRC) components in neural induction.
- To determine the specific function of Polyhomeotic Homolog 1 (Phc1) in neural differentiation.
- To understand the epigenetic mechanisms underlying Phc1-mediated neural development.
Main Methods:
- Utilized mouse embryonic stem (ES) cell differentiation system.
- Generated and analyzed Phc1-knockout (Phc1-KO) ES cells.
- Performed chromatin accessibility analysis.
- Examined gene expression of PRC components and BMP signaling pathway.
Main Results:
- Phc1-KO ES cells failed to achieve neural fate, remaining pluripotent or in primitive non-neural states.
- Phc1 is essential for proper chromatin packing, as indicated by accessibility analyses.
- Phc1 deficiency led to aberrant upregulation of BMP signaling in mutant embryos.
Conclusions:
- Phc1 plays a critical role in neural differentiation through epigenetic regulation.
- Phc1 is required for maintaining appropriate chromatin structure during neural development.
- Dysregulation of Phc1 impacts BMP signaling, underscoring its importance in neural fate commitment.
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