从iPSC衍生的星细胞和神经元复制大脑基因表达,表观遗传,细胞形态和连接性变化在自闭症中发现
Hamid Mostafavi Abdolmaleky1,2, Reza Alam1, Shabnam Nohesara2
1Nutrition/Metabolism Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cells
|July 12, 2024
概括
自闭症涉及炎症和氧化压力,影响表观遗传学. 诱导多能干细胞衍生细胞反映了这些大脑变化,为个性化自闭症疗法提供了潜力.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 自闭症谱系障碍 (ASD) 的特点是过度的炎症和氧化应激,这会影响表观遗传的情景.
- 目前对ASD的治疗策略是有限的,因为缺乏患者特异的脑分子标记物以进行个性化治疗.
研究的目的:
- 调查自闭症患者的诱导多能干细胞 (iPSC) 衍生神经元和星体是否复制死后大脑表达和表观遗传变化.
- 评估iPSC衍生细胞作为研究自闭症发病因子和开发患者特异性治疗方法的模型的实用性.
主要方法:
- 从5名自闭症患者和5名对照人群中产生了iPSC衍生的神经元和星球细胞.
- 在iPSC衍生的细胞中分析了基因表达和DNA甲基化模式.
- 结果与来自10个死后大脑样本 (5个自闭症,5个对照组) 的DNA甲基化数据进行比较.
主要成果:
- 自闭症iPSC衍生天体细胞显示了包括TGFB1,TGFB2,IL6,IFI16,HAP1,SIRT1,NURR1,RELN,GPX1,EN2,SLC1A2和SLC1A3.3在内的基因的改变表达.
- 表观遗传变化,包括DNA低甲基化和改变的5-甲基化,在自闭症iPSC衍生的星体和神经元中的基因促进体 (例如TGFB2,IL6,TNFA,EN2,HAP1) 中观察到.
- 在自闭症iPSC模型中,神经元形态减少了,而星细胞大小增加了;死后的大脑样本证实了TGFB2,IFI16,HAP1和SLC1A2.2中的DNA甲基化变化.
结论:
- 从iPSC衍生的神经元和星细胞准确地复制自闭症相关表达和死后脑组织中发现的表观遗传变化.
- 这些iPSC衍生细胞作为研究自闭症病原学的有价值的替代体.
- 这些发现支持使用iPSC衍生细胞开发自闭症个性化治疗方法的潜力.
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