人类iPSC衍生的金字塔神经元的功能成熟在体内取决于与宿主组织的接近
Célia Raïs1,2, Daniela Gaspar Santos1,2, Giulia Sansone1
1Institut Pasteur, Université de Paris Cité, Unité Neurobiologie Intégrative des Systèmes Cholinergiques, CNRS UMR 3571 "Genes, Synapses and Cognition," Paris, France.
Frontiers in cellular neuroscience
|December 11, 2023
概括
移植到小鼠大脑中的人类诱导多能干细胞 (hiPSCs) 显示出类似胚胎的神经活动和突触发育. 这个模型有助于研究神经发育障碍,如精神分裂症和自闭症谱系障碍.
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
- 发展生物学 发展生物学
背景情况:
- 人类诱导的多能干细胞 (hiPSCs) 对体外神经发育建模具有价值.
- 在大脑中的hiPSCs的体内应用面临挑战,但具有显著的潜力.
- 之前的研究强调需要强大的方法来分析体内移植的神经细胞.
研究的目的:
- 开发和验证一种系统的方法来分析随着时间的推移移植到小鼠大脑中的hiPSC衍生神经和质细胞.
- 描述这些移植细胞的体内功能活动和突触发育.
- 建立一个平台来研究神经发育性疾病使用hiPSC衍生细胞 in vivo.
主要方法:
- 将hiPSC衍生的神经和质细胞移植到小鼠大脑中.
- 对表达GCaMP6f的人类神经细胞进行功能双光子成像,以评估自发活动.
- 详细电子显微镜 (EM) 检查移植结构和突触发育.
- 在移植后7个月内对细胞行为和整合进行纵向分析.
主要成果:
- 在移植的人类神经细胞中的胚胎类自发活动的量化.
- 对移植的详细超结构分析,包括突触结构.
- 在高PSC衍生神经元中持续突触发育的证明,在体内长达7个月.
- 移植细胞在小鼠大脑环境中的成功整合和生存.
结论:
- 移植的hiPSC衍生神经细胞表现出类似胚胎的活动,并在小鼠大脑中发生突触发育.
- 这种体内系统为研究神经发育过程和疾病提供了一个强大的平台.
- 该方法使未来的遗传或实验操纵能够用于疾病建模,例如精神分裂症和自闭症谱系障碍.
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