孤儿核受体TLX在成年神经干细胞中的表达和功能
Yanhong Shi1, D Chichung Lie, Philippe Taupin
1Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|January 1, 2004
概括
核受体TLX (Toll-like受体4) 对于维持成年神经干细胞至关重要. 丧失TLX会损害干细胞的增殖和分化,影响大脑功能.
科学领域:
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 神经发生,新神经元的产生,发生在成人大脑中,导致发现成人神经干细胞.
- TLX (Toll-like receptor 4) 是一个孤儿核受体,在成年大脑中高度表达.
- TLX-null小鼠表现出神经和行为缺陷,这表明在成人大脑功能中发挥了作用.
研究的目的:
- 研究TLX在维持成年神经干细胞中的作用.
- 确定TLX是否对神经干细胞的增殖,自我更新和分化至关重要.
主要方法:
- 光激活细胞分类 (FACS) 用于从成年大脑中分离TLX表达和TLX无细胞.
- 实验室内增殖,自我更新和分化试验是在孤立的细胞上进行的.
- 在TLX突变小鼠的体内研究评估了神经原生区域的细胞增殖和巢素标记.
- 对质纤维酸蛋白 (GFAP) 表达进行了分析,以了解TLX的调节机制.
主要成果:
- 从成年大脑中分离出来的TLX表达细胞在体外表现出增殖,自我更新和分化为所有神经细胞类型.
- 在体外,TLX-null细胞未能繁殖,而重新引入TLX可以挽救这种缺陷.
- 突变TLX的小鼠在成年神经原生区域表现出细胞增殖和内斯标记的减少.
- 证实TLX能够沉默神经干细胞中的GFAP表达,这表明TLX在通过转录抑制来维持它们的无差异状态方面发挥了作用.
结论:
- TLX对于保持成年神经干细胞在未分化和增殖状态至关重要.
- 通过调节神经干细胞行为,TLX在成人神经发生过程中发挥着至关重要的作用.
- 通过TLX进行转录抑制可能是保持神经干细胞未分化的关键机制.
相关概念视频
01:24Methods of Nuclear Reprogramming
2.3K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.3K
02:39lncRNA - Long Non-coding RNAs
10.2K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
10.2K
01:26Stem Cell Niche
6.6K
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
6.6K
02:23Master Transcription Regulators
8.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.6K
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...
2.6K
01:16TGF - β Signaling Pathway
10.9K
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...
10.9K