Sirt6 regulates the proliferation of neural precursor cells and cortical neurogenesis in mice

Yufei Wei; Xinhuan Wang; Zhihua Ma; Pan Xiang; Gaoao Liu; Bin Yin; Lin Hou; Pengcheng Shu; Wei Liu; Xiaozhong Peng

doi:10.1016/j.isci.2023.108706

Sirt6 regulates the proliferation of neural precursor cells and cortical neurogenesis in mice

iScience. 2023 Dec 9;27(2):108706. doi: 10.1016/j.isci.2023.108706. eCollection 2024 Feb 16.

Authors

Yufei Wei¹, Xinhuan Wang¹, Zhihua Ma¹, Pan Xiang¹, Gaoao Liu¹, Bin Yin¹, Lin Hou¹, Pengcheng Shu¹, Wei Liu¹, Xiaozhong Peng^{1

2

3

4}

Affiliations

¹ State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
² Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
³ Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
⁴ State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

Abstract

Sirt6, a member of the class III histone deacetylases (HDACs), functions in the regulation of genomic stability, DNA repair, cancer, metabolism and aging. Sirt6 deficiency is lethal, and newborn SIRT6-null cynomolgus monkeys show unfinished brain development. After the generation of a cortex-specific Sirt6 conditional knockout mouse model, we investigated the specific deletion of Sirt6 in NPCs at E10.5. This study found that Sirt6 deficiency causes excessive proliferation of neural precursor cells (NPCs) and retards differentiation. The results suggest that endogenous Sirt6 in NPCs regulates histone acetylation and limits stemness-related genes, including Notch1, in order to participate in NPC fate determination. These findings help elucidate Sirt6's role in brain development and in NPC fate determination while providing data on species generality and differentiation.

Keywords: Biological sciences; developmental genetics; developmental neuroscience.