在受伤后从SVZ处进行保护性星体生成,由Notch调制器Thbs4控制
Eric J Benner1, Dominic Luciano, Rebecca Jo
1George and Jean Brumley Neonatal-Perinatal Research Institute, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Nature
|April 26, 2013
概括
大脑中的神经干细胞 (NSCs).
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
- 质生物学 质生物学
背景情况:
- 产后/成年神经干细胞 (NSCs) 在下腹部区域 (SVZ) 产生神经母细胞,用于嗅球.
- SVZ NSCs也可以分化为星体细胞,但有利于星体生成而不是神经生成的条件尚不清楚.
- 与其他大脑天体细胞相比,SVZ衍生的天体细胞的特性尚未得到充分理解.
研究的目的:
- 在SVZ的利基市场中,研究有利于天体生成而不是神经生成的条件.
- 描述SVZ衍生的星形细胞及其在脑损伤中的作用.
- 阐明调节受伤后SVZ星体生成的分子机制.
主要方法:
- 使用了受他莫西芬诱导的nestin-creER(tm) 4血统追踪的小鼠.
- 在SVZ衍生天体细胞中研究了血栓素4 (Thbs4) 表达.
- 研究了Thbs4和Notch信号在光血栓/缺血性皮质损伤后的SVZ星化中的作用.
- 分析了Thbs4同卵性淘汰赛 (Thbs4(KO/KO)) 小鼠的伤害后细胞和功能缺陷.
主要成果:
- 由SVZ生成的星体细胞表达高水平的血栓素4 (Thbs4),与皮质星体细胞不同.
- 皮质损伤显著增加了来自SVZ利基的Thbs4 ((hi) 天体细胞产量.
- 由SVZ衍生的Thbs4(hi) 星体,而不是神经母细胞,迁移到受伤的皮质,需要由Thbs4.4调节的Notch激活.
- Thbs4淘汰赛小鼠表现出SVZ天体生成受损,神经细胞向损伤部位迁移增加,质痕异常和微血管出血.
结论:
- 血栓素4 (Thbs4) 在皮层损伤后将SVZ神经干细胞 (NSC) 引导向星体生成方面发挥着关键作用.
- Thbs4介导的Notch激活对于损伤后的质反应和适当的质痕形成至关重要.
- Thbs4的失调影响NSC的命运,导致异常的细胞反应和增加的大脑损伤,对治疗策略有影响.
相关概念视频
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...
01:12Role 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...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
02:33Hedgehog Signaling Pathway
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...
01:16TGF - β Signaling Pathway
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 are of three kinds RI, RII, and RIII. The RI...