相关实验视频
Updated: Jun 16, 2025

09:41
Reconstitution Of β-catenin Degradation In Xenopus Egg Extract
Published on: June 17, 2014
12.1K
ALKBH5通过调节DKK1/4介导的Wnt/β-catenin激活来控制人类内皮的命运
Zechuan Liang1,2, Tao Huang1,2, Wei Li3,4
1College of Life Sciences, Zhejiang University, Hangzhou, China.
Nucleic acids research
|August 21, 2024
概括
m6A脱甲基酶ALKBH5对于人类胚胎干细胞的分化至关重要. 它的缺失会通过影响GATA6mRNA稳定性和Wnt信号来损害内皮的形成.
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.
- 干细胞生物学 干细胞生物学
- 发展生物学 发展生物学
背景情况:
- N6-甲基氨酸 (m6A) 是哺乳动物中普遍存在的mRNA修饰.
- 在早期人类发育中m6A的作用仍然不完全理解.
研究的目的:
- 研究m6A脱甲基酶ALKBH5在人类胚胎干细胞 (hESC) 分化中的功能.
- 阐明ALKBH5调节内皮形成的分子机制.
主要方法:
- 在CRISPR-Cas9基因编辑中生成ALKBH5淘汰hESCs.
- 终极内皮 (DE) 分化效率的分析.
- RNA免疫沉降测序 (RIP-seq) 和mRNA稳定性测试.
- 定量PCR和西式斑点测试用于评估基因和蛋白质表达.
主要成果:
- 在hESC中ALKBH5删除严重损害了DE分化和原始条纹 (PS) 过渡.
- ALKBH5 缺乏导致 GATA6 mRNA 过甲基化和通过 YTHDF2.2. 的破坏稳定.
- GATA6调节Wnt/β-catenin信号对抗剂DKK1和DKK4,这些对抗剂在ALKBH5-/- hESC中被抑制.
- DKK1和DKK4被确定为下游目标,调节DE形成所必需的Wnt信号.
结论:
- 在人体内皮肤内皮形成过程中,ALKBH5在体外发挥着至关重要的作用.
- ALKBH5通过控制GATA6mRNA稳定性和Wnt/β-catenin信号传递来调节DE的分化.
- 这项研究揭示了ALKBH5的新功能,其下游目标DKK1/4在早期人类胚胎发生过程中.
相关概念视频
Canonical Wnt Signaling Pathway
8.7K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
Non-Canonical Wnt Signaling Pathways
7.3K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K
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
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Hedgehog Signaling Pathway
7.3K
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...
7.3K
TGF - β Signaling Pathway
7.3K
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...
7.3K

