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Differentiation of Mouse Embryonic Stem Cells into Cortical Interneuron Precursors
Published on: December 3, 2017
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c-Rel Regulates Inscuteable Gene Expression during Mouse Embryonic Stem Cell Differentiation
Riki Ishibashi1, Satoshi Kozuki1, Sachiko Kamakura2
1From the Department of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan, the Department of Mammalian Regulatory Networks, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan, and.
The Journal of Biological Chemistry
|December 24, 2015
Summary
Mouse embryonic stem cell differentiation involves Inscuteable (Insc) gene expression. The transcription factor c-Rel promotes Insc expression, influencing mesodermal cell fate during differentiation.
Area of Science:
- Stem cell biology
- Developmental biology
- Gene regulation
Background:
- Inscuteable (Insc) plays a critical role in stem cell fate decisions, balancing symmetric and asymmetric cell division.
- Regulation of mouse Insc gene expression is not well understood, despite its importance in stem cell division.
- Mouse embryonic stem (mES) cells differentiate into bipotent mesendoderm, producing both endoderm and mesoderm.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling mouse Insc gene expression during mES cell differentiation.
- To identify the transcriptional regulatory elements and factors involved in mouse Insc transcription.
- To elucidate the role of c-Rel in regulating mouse Insc expression and its impact on cell fate decisions.
Main Methods:
- Identification of a minimal transcriptional regulatory element for mouse Insc in mES cells.
- Chromatin immunoprecipitation (ChIP) assays to determine transcription factor binding.
- Short interfering RNA (siRNA)-mediated knockdown and overexpression studies to assess gene function.
- Flow cytometry or similar methods to quantify cell populations and differentiation outcomes.
Main Results:
- A minimal transcriptional regulatory element driving mouse Insc transcription was identified upstream of the transcription start site.
- The transcription factor c-Rel was found to bind this element and promote mouse Insc expression in mES cells.
- Knockdown of mouse INSC or c-Rel reduced mesodermal cell populations but did not affect mesendoderm or endoderm differentiation.
- Overexpression of mouse INSC rescued the mesoderm-deficient phenotype caused by c-Rel knockdown.
Conclusions:
- Mouse Insc expression is transiently upregulated during early mES cell differentiation into mesendoderm.
- The transcription factor c-Rel directly promotes mouse Insc expression by binding to a specific regulatory element.
- Regulation of mouse Insc by c-Rel is crucial for proper mesodermal cell fate determination during mES cell differentiation.
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