Acquisition of neural fate by combination of BMP blockade and chromatin modification

Agnes Lee Chen Ong; Toshiya Kokaji; Arisa Kishi; Yoshihiro Takihara; Takuma Shinozuka; Ren Shimamoto; Ayako Isotani; Manabu Shirai; Noriaki Sasai

doi:10.1016/j.isci.2023.107887

Acquisition of neural fate by combination of BMP blockade and chromatin modification

iScience. 2023 Sep 9;26(10):107887. doi: 10.1016/j.isci.2023.107887. eCollection 2023 Oct 20.

Authors

Agnes Lee Chen Ong¹, Toshiya Kokaji², Arisa Kishi¹, Yoshihiro Takihara³, Takuma Shinozuka¹, Ren Shimamoto¹, Ayako Isotani¹, Manabu Shirai⁴, Noriaki Sasai¹

Affiliations

¹ Division of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma 630-0192, Japan.
² Data-driven biology, NAIST Data Science Center, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma 630-0192, Japan.
³ Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-0037, Japan.
⁴ Omics Research Center (ORC), National Cerebral and Cardiovascular Center, 6-1 Kishibe Shinmachi, Suita, Osaka 564-8565, 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.

Keywords: Epigenetics; Molecular biology; Neuroscience; Stem cells research; Transcriptomics.