Dr. LIU Pingyu and colleagues led by Prof. JING Naihe at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, have reported the key role and the underlying mechanism of histone deacetylation in the regulation of the mouse neural induction.
The formation of the neuroectoderm, termed neural induction or neural fate commitment, is the first step in the development of the central nervous system and initiates at approximately embryonic day (E) 7.0. Cell fate determination requires the cooperation between extrinsic signals and intrinsic molecules including transcription factors as well as epigenetic regulators. Nevertheless, how neural fate commitment is regulated by epigenetic modifications remains largely unclear.
Dr. LIU Pingyu and others found that the histone deacetylation at the epiblast stage promoted neural differentiation of mouse embryonic stem cells (mESCs). HDAC1 (Histone deacetylase 1) deficiency in mESCs partially phenocopied the inhibition of histone deacetylation in vitro, and displayed reduced incorporation into neural tissues in chimeric mouse embryos in vivo. Mechanistic studies demonstrated that Nodal, which is repressed by histone deacetylation, is a direct target of HDAC1. Furthermore, the inhibition of histone deacetylation in the anterior explant of mouse embryos at E7.0 led to Nodal activation and neural development repression. Their study reveals a novel intrinsic mechanism that epigenetic histone deacetylation ensures neural fate commitment by restricting Nodal signaling in early mouse anterior epiblast ex vivo and mESC in vitro. Their work also provides mechanistic insights and therapeutic applications for the efficient derivation of human pluripotent stem cell-differentiated functional neural progenitors for potential regenerative medicine.
This study entitled “Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate” was published online in Nature Communications on April, 23, 2015.
This work was in collaboration with Prof. LI Jinsong at SIBCB and Prof. HAN Jingdong at PICB, and funded by the "Strategic Priority Research Program" of the Chinese Academy of Sciences, the National Key Basic Research and Development Program of China, and the National Natural Science Foundation of China.
CONTACT:
JING Naihe, Principal Investigator
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shanghai 200031, China.
Tel.: +86-21-5492-1381;
Fax: +86-21-5492-1011;
E-mail: njing@sibcb.ac.cn
Fig. A model of the regulation of Nodal expression by histone deacetylation during neural fate determination. (Image provided by Dr. JING Naihe’s group)
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