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Acquisition of Neural Fate by Combination of BMP Blockade and Chromatin Modification

52 Pages Posted: 7 Jun 2023 Publication Status: Published

See all articles by Agnes Lee Chen Ong

Agnes Lee Chen Ong

Nara Institute of Science and Technology - Division of Biological Science

Toshiya Kokaji

Nara Institute of Science and Technology - Data-driven biology

Arisa Kishi

Nara Institute of Science and Technology - Division of Biological Science

Yoshihiro Takihara

Hiroshima University - Research Institute for Radiation Biology and Medicine

Takuma Shinozuka

Nara Institute of Science and Technology - Division of Biological Science

Ren Shimamoto

Nara Institute of Science and Technology - Division of Biological Science

Ayako Isotani

Nara Institute of Science and Technology - Division of Biological Science

Manabu Shirai

National Cerebral and Cardiovascular Center Research Institute - Omics Research Center

Noriaki Sasai

Nara Institute of Science and Technology - Division of Biological Science

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Abstract

Neural induction is a process where naïve cells are converted into committed cells with neural characteristics, and occurs at the earliest step during embryogenesis. Although the molecular mechanisms of neural induction, such as signal molecules and chromatin remodelling, have been identified, the correlations between these events 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 at pluripotent or primitive non-neural states. A chromatin accessibility analysis suggests that Phc1 is essential for chromatin packing. The aberrant upregulation of the BMP signal was confirmed in the Phc1 homologous mutant embryos. Taken together, Phc1 is required for neural differentiation through epigenetic modification.

Note:

Funding Information: This work was supported in part by grants-in-aid for scientific research from the Japan Society for the Promotion of Science (JP21K16349 to TK; 21H02889 to MS; 19H04781 and 20H03263 to NS)

Declaration of Interests: The authors declare no conflict of interest.

Ethical Approval Statement: All animal experiments were performed under the approval of the Animal Welfare and Ethical Review Panel of Nara Institute of Science and Technology (approval numbers of 1810 and 2311) with the protocols in accordance with the national and internal regulations.

Suggested Citation

Ong, Agnes Lee Chen and Kokaji, Toshiya and Kishi, Arisa and Takihara, Yoshihiro and Shinozuka, Takuma and Shimamoto, Ren and Isotani, Ayako and Shirai, Manabu and Sasai, Noriaki and Administrator, Sneak Peek, Acquisition of Neural Fate by Combination of BMP Blockade and Chromatin Modification. Available at SSRN: https://ssrn.com/abstract=4470116 or http://dx.doi.org/10.2139/ssrn.4470116
This version of the paper has not been formally peer reviewed.

Agnes Lee Chen Ong

Nara Institute of Science and Technology - Division of Biological Science ( email )

Toshiya Kokaji

Nara Institute of Science and Technology - Data-driven biology ( email )

Arisa Kishi

Nara Institute of Science and Technology - Division of Biological Science ( email )

Yoshihiro Takihara

Hiroshima University - Research Institute for Radiation Biology and Medicine ( email )

Takuma Shinozuka

Nara Institute of Science and Technology - Division of Biological Science ( email )

Ren Shimamoto

Nara Institute of Science and Technology - Division of Biological Science ( email )

Ayako Isotani

Nara Institute of Science and Technology - Division of Biological Science ( email )

Manabu Shirai

National Cerebral and Cardiovascular Center Research Institute - Omics Research Center ( email )

Noriaki Sasai (Contact Author)

Nara Institute of Science and Technology - Division of Biological Science ( email )

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