不同的Notch信号区分神经干细胞从中间的祖先
Ken-ichi Mizutani1, Keejung Yoon, Louis Dang
1Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature
|August 28, 2007
概括
神经干细胞 (NSC) 和中介神经祖先 (INP) 不同地使用Notch信号. CBF1活动区分这些细胞,NSCs表现出更高的活动,影响它们在大脑发育期间的分化潜力.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 大脑发育涉及神经干细胞 (NSC) 和中介神经祖先 (INP),产生神经元和神经质.
- 区分NSC和INP的信号通路尚未完全理解.
- 痕信号保持NSC特征并抑制神经发生,但其在INP中的作用尚不清楚.
研究的目的:
- 调查Notch信号及其效应因子C-促进剂结合因子1 (CBF1) 在区分NSC和INP中的作用.
- 确定CBF1活动如何影响NSC和INP的命运和差异化潜力.
- 探索CBF1作为干细胞与祖细胞的一般标记物的潜力.
主要方法:
- 使用体内记者测试 (转基因和过渡性) 来监测NSC和INP中的CBF1活性.
- 在神经前细胞中进行CBF1的淘汰和激活实验.
- 进行了体内移植试验,以评估NSC和INP的分化潜力.
主要成果:
- 无论是NSC还是INP,都对Notch受体激活有反应,但表现出差异性的CBF1信号传递.
- NSC显示强大的CBF1信号,而INP则减弱了CBF1活动.
- CBF1的淘汰促使NSC转换为INP,但CBF1的激活不会将INP转换回NSC.
- NSC和INP共存于脑心室区域,可以根据CBF1活动进行分离.
- NSCs产生神经元,星球细胞和寡细胞,而INP主要是神经性.
结论:
- 在Notch信号下游的CBF1活动是NSC和INP之间的关键差异.
- CBF1信号传递在维持NSC身份和影响祖先分化方面发挥着至关重要的作用.
- 对CBF1级联的差异化利用可能是一个普遍的机制,可以在各种组织中区分干细胞和祖细胞.
相关概念视频
01:51Determination
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:26Stem Cell Niche
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...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
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...