Sirt6 Regulates the Proliferation of Neural Precursor Cells and Cortical Neurogenesis in Mice

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jan 30

PMID 38288355

Authors

Yufei Wei

Xinhuan Wang

Zhihua Ma

Pan Xiang

Gaoao Liu

Bin Yin

Lin Hou

Pengcheng Shu

Wei Liu

Xiaozhong Peng

Affiliations

Soon will be listed here.

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.

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