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

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.