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相关概念视频

Cadherins in Tissue Organization01:19

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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.
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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...
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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
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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.
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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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在神经元分化过程中,CHD7与绝缘体结合.

Jingyun Qiu1,2, Azadeh Jadali3, Edward Martinez1,2

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概括

染色体重塑器CHD7对于螺旋质神经元 (SGN) 的分化至关重要,对听力至关重要. 这项研究揭示了CHD7.

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科学领域:

  • 神经科学是一个神经科学.
  • 遗传学 是一个遗传学.
  • 干细胞生物学 干细胞生物学

背景情况:

  • 螺旋质神经元 (SGN) 对于听力至关重要;它们的丧失导致听力损失.
  • 了解SGN分化机制对于开发基于干细胞的再生疗法至关重要.
  • 染色体重塑剂,如CHD7,在SGN发育中的作用尚未完全理解.

研究的目的:

  • 为了研究染色体重塑剂CHD7在眼睛前代细胞神经元分化中的功能.
  • 阐明CHD7影响基因调节在cis-regulatory元素中的机制.
  • 探索针对CHD7相关的调节区域以促进神经元分化的潜力.

主要方法:

  • 利用不朽化的多能眼前生细胞 (iMOP) 来研究神经元分化.
  • 进行了CHD7的淘汰实验,以评估其对差异化的影响.
  • 进行了全基因组分析,以确定CHD7结合位点和CTCF丰富在拓关联域边界.
  • 使用CRISPR干扰 (CRISPRi) 和CRISPR激活 (CRISPRa) 来操纵特定调节区域的基因表达.

主要成果:

  • 在iMOP细胞中显著损害神经元分化.
  • 全基因组分析揭示了CHD7和CTCF在TAD之间位于绝缘体元素的共同占用.
  • 针对这些调节区域,特别是在MIR9-2基因附近,通过CRISPRi和CRISPRa增强了miR-9转录.
  • 有证据表明,这些CHD7/CTCF标记的元素作为调节基因表达的绝缘体起作用.

结论:

  • CHD7在促进SGN差异化方面发挥着关键作用,这对听力至关重要.
  • CHD7在绝缘体元素中发挥作用,通常由CTCF标记,以调节参与神经元发育的基因.
  • 这项研究揭示了一种涉及CHD7和绝缘体促进神经元分化的新机制,提供了治疗见解.