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相关概念视频

EPS and iPS Cells in Disease Research01:21

EPS and iPS Cells in Disease Research

Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...

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The Specification of Telencephalic Glutamatergic Neurons from Human Pluripotent Stem Cells
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胚胎干细胞衍生的神经元作为在发育过程中表观基因组成熟的模型系统.

Sally Martin1,2, Daniel Poppe3,4, Nelly Olova5

  • 1Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.

Genes
|May 27, 2023
PubMed
概括
此摘要是机器生成的。

来自干细胞的小鼠神经元可以在体内复制DNA甲基化模式,与人类神经元不同. 这一突破允许在体外研究神经元表观基因组成熟.

关键词:
通过DNA甲基化.细胞培养系统细胞培养系统在表观基因组学上,表观基因组学.神经元成熟的过程神经科学 神经科学

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科学领域:

  • 神经科学是一个神经科学.
  • 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
  • 发展生物学 发展生物学

背景情况:

  • DNA甲基化,特别是在CH序列环境 (mCH) 中,对于神经元基因组调节和成熟至关重要.
  • 脊椎动物的神经元在出生后早期的大脑发育期间表现出独特的高水平的mCH,与其他组织不同.

研究的目的:

  • 评估来自小鼠和人类多能干细胞的体外衍生神经元在体内模仿DNA甲基化模式的能力.
  • 建立一个可处理的体外模型来研究神经元表观基因组成熟.

主要方法:

  • 人类和小鼠胚胎干细胞 (ESC) 衍生的神经元在2D和3D器官中培养的DNA甲基化模式的比较与体内发育.
  • 对DNA甲基转移酶Dnmt3a表达的分析,转移后标记物Rbfox3 (NeuN) 时间和mCH沉积的局部化.
  • 在mCH和基因表达之间进行相关性分析.

主要成果:

  • 人类ESC衍生的神经元未能在体外积累mCH,无论培养模型 (2D或3D).
  • 鼠标ESC衍生的皮质神经元在体外成功获得了mCH的体内水平,反映了发育时间.
  • 鼠标神经元中的mCH沉积与Dnmt3a增加相关,随后Rbfox3表达,局部化到核膜,并对基因表达产生负面影响.

结论:

  • 鼠标ESC衍生的神经元作为一个可行的体外模型来复制神经元DNA甲基化格局,与人类对应物不同.
  • 这种模型系统能够在实验可处理的时间框架内对表观基因组成熟进行实验性研究.
  • 甲基化模式的微妙差异表明非细胞自主因素在体内神经元表观基因组中具有影响.