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多种因素有助于人类衍生的诱导多能干细胞有效地分化为中脑多巴胺基神经元

Yalan Chen¹, Junxin Kuang², Yimei Niu¹

¹Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China.

Neural regeneration research

|October 16, 2023

概括

科学家们开发了三个协议,从干细胞产生中脑多巴胺基神经元. 结合CHIR,SHH和FGF8的方法产生了这些关键神经元的最高比例,用于疾病研究和治疗.

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:

中脑多巴胺基神经元在神经发育和神经退行性疾病中至关重要.
这些神经元是细胞移植疗法的潜在来源.
研究它们的功能障碍需要可访问的体外模型.

研究的目的:

从人类诱导的多能干细胞 (hiPSCs) 来产生中脑多巴胺基神经元的高效协议.
为了优化神经诱导和分化用于治疗应用.
研究提高功能性多巴胺基神经元产量的方法.

主要方法:

使用SB431542和dorsomorphin进行初始的神经诱导.
集成的声波刺 (SHH) 和纤维细胞生长因子8 (FGF8) 来增强多巴胺基神经元的产生.
应用CHIR99021 (CHIR) 小分子抑制剂,以进一步优化分化协议.

主要成果:

最初的诱导产生了20%的氨酸氧化酶阳性 (TH +) 多巴氨基神经元.
添加SHH和FGF8将TH+神经元增加到75%,其中15%共表达FOXA2.2.
通过CHIR,SHH和FGF8的联合方案,中脑中多巴胺基神经元的TH+/FOXA2+生成率达到31-74%.

结论:

成功建立了诱导多巴胺基神经元的三个不同的协议.
结合的CHIR,SHH和FGF8协议显著增强了中脑多巴胺基神经元的产生.
这种优化的协议为研究和治疗中脑相关疾病提供了宝贵的资源.

关键词:

在FGF信号信号.这是一个SHH信号.这是一个SMAD信号.这是一个WNT信号.多巴胺类神经元的神经元诱导多能干细胞的诱导干细胞.中间大脑中间大脑神经分化的神经分化.

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