人类诱导多能干细胞衍生天体细胞缺乏脆弱的X信使核蛋白生成和表征
Bharath Kumar Reddy1, Nikhita Annaiyappa2, Aditi Bhattacharya2
1Centre for High Impact Neuroscience and Translational Applications, TCG Centres for Research and Education in Science and Technology; Academy of Scientific and Innovative Research (AcSIR).
Journal of visualized experiments : JoVE
|June 23, 2025
概括
脆弱X综合征 (FXS) 天体细胞表现出代谢失调. 这项研究开发了一种人类干细胞模型,以调查神经发育障碍中的FXS相关的星细胞功能障碍.
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
- 发育生物学 发展生物学
背景情况:
- 脆弱X综合征 (FXS) 是自闭症谱系障碍和智力障碍的主要遗传原因.
- 以前的FXS研究主要使用动物模型,专注于神经元,忽视了质细胞的作用.
- 了解恒星细胞参与FXS对于全面了解神经发育障碍至关重要.
研究的目的:
- 开发一种基于人类干细胞的模型,用于研究FXS中的天体细胞发育和功能.
- 研究FXS对人类天体细胞成熟和新陈代谢的影响.
- 建立一个框架,探索细胞自主和非细胞自主作用在FXS相关的神经发育障碍.
主要方法:
- 人类诱导的多能干细胞被用SMAD抑制和小分子模拟成神经ectoderm.
- 天体细胞原生细胞 (APC) 由对照细胞和来自FXS患者的干细胞生成.
- 使用纤毛神经变因子将APC分化为前脑星细胞,并评估其代谢功能.
主要成果:
- 建立了一个协议,从干细胞中产生功能性人类星体细胞,捕获关键的发育和质生成里程碑.
- 与对照组相比,来自FXS患者的星体细胞显示了糖分和线粒体代谢的失调.
- 生成的星体细胞显示功能性对ATP的反应,证实了它们的生存能力.
结论:
- 这项研究提出了一种新的人类干细胞衍生模型,用于研究星系细胞对FXS的贡献.
- 这些发现突出了FXS星形细胞中的代谢异常,表明它在疾病的病理生理学中发挥了作用.
- 开发的模型作为未来研究影响质功能的神经发育障碍的宝贵平台.
相关概念视频
01:58X-Inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
02:50Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
01:24Methods of Nuclear Reprogramming
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01:28Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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01:24B Cell Activation and Differentiation
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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