GID复合体通过破坏TET2的稳定性来调节神经干细胞的分化
Meiling Xia1,2, Rui Yan2, Wenjuan Wang2
1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Frontiers of medicine
|September 14, 2023
概括
葡萄糖诱导的降解缺陷 (GID) 综合体向十一转位2 (TET2) 降解,影响神经干细胞分化和大脑发育.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发展生物学 发展生物学
- 分子神经科学 分子神经科学
背景情况:
- 神经干细胞 (NSC) 的分化需要精确的基因表达调节.
- 十-十一转位2 (TET2) 是一个表观遗传因子,对神经元差异化至关重要.
- 在NSC分化过程中调节TET2的机制在很大程度上是未知的.
研究的目的:
- 阐明在NSC分化过程中控制TET2蛋白水平的调控机制.
- 为了研究在TET2调节中泛素-蛋白酶体通路的作用.
- 确定涉及TET2介导大脑发育的新型因素.
主要方法:
- 西方涂抹用于评估TET2和GID复杂子单元的蛋白质和mRNA水平.
- 同免疫沉以确认TET2和GID复合体之间的物理相互作用.
- 通过RNA干扰 (siRNA) 来使GID复杂子单元保持沉默 (WDR26,ARMC8).
- 对5-基甲基细胞素水平的分析.
- 对NSC差异化标记的评估.
- 在Wdr26+/-小鼠中对TET2水平的基因型化和分析.
主要成果:
- 在NSC分化过程中,TET2蛋白水平下降,而mRNA水平在NSC分化过程中保持稳定,表明转录后调节.
- TET2在物理上与葡萄糖诱导的降解缺陷 (GID) 基酶复合体相互作用,并被基化.
- 静止GID复杂子单元 (WDR26,ARMC8) 减少了TET2的泛化和降解,增加了全球5甲基细胞素水平,并促进了NSC分化.
- 在Wdr26+/-小鼠的大脑中,TET2蛋白水平升高.
结论:
- GID 泛基因酶复合体通过泛基因化和蛋白质体降解来负面调节 TET2 蛋白质的稳定性.
- 这种GID复杂介导的TET2调节是一种控制NSC分化和大脑发育的新机制.
更多相关视频
09:19Author Spotlight: Improved Nucleofection for High-Efficiency Gene Delivery in Murine Subventricular Zone-Derived Neural Stem Cell Cultures
Published on: June 14, 2024
2.4K
10:25Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
Published on: December 12, 2019
7.7K
相关概念视频
Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
Maintenance of the ES Cell State
2.2K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.2K
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Destabilization of Microtubules
2.8K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.8K
Cadherins in Tissue Organization
3.0K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.0K
