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用转录因子对小鼠和人类纤维细胞进行神经重编程,这些转录因子涉及到上体核发育的过程

Masatoshi Hirayama^1,2, Ludovic S Mure^1,3,4, Hiep D Le¹

¹Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.

|February 22, 2024

概括

科学家们通过使用特定的转录因子,从纤维细胞中产生了血管活性肠道多 (VIP) 神经元. 这一突破为未来的Suprachiasmatic Nucleus (SCN) 再生和体外疾病建模提供了潜力.

科学领域:

神经科学是一个神经科学.
发展生物学发展生物学
细胞生物学细胞生物学

背景情况:

超性核 (SCN) 通过各种神经元调节昼夜节律,包括表达血管活性肠道多 (VIP) 和氨酸压素 (AVP) 的神经元.
在SCN中的神经元亚型通过神经发生过程中的特定转录因子 (TF) 表达而发展.
在实验室中生成SCN神经元一直是一个重大挑战.

研究的目的:

为了实现SCN神经元的体外生成,特别是VIP表达神经元.
研究关键转录因子在SCN神经发生和神经元亚型规范中的作用.
探索SCN再生和体外疾病建模的潜力.

主要方法:

使用了一种高效的神经元转换协议.
补充了转录因子Six3,Six6,Dlx2和Lhx1的协议,已知在SCN神经发生过程中表达.
从小鼠和人类纤维细胞诱导的神经元转换.

主要成果:

从纤维细胞成功生成了神经元,这些神经元具有神经元特性.
诱导的神经元显示双极或多极形态.
诱导的神经元中有很大一部分是GABAergic,表达VIP,这是SCN神经元的特征.

结论:

研究的转录因子 (Six3, Six6, Dlx2, Lhx1) 对表达VIP的神经元的发展至关重要.
这种方法证明了在体外产生特定SCN神经元亚型的潜力.
这些发现表明,未来的SCN再生和体外疾病建模有望成为未来的途径.

关键词:

细胞生物学细胞生物学分子生物学分子生物学神经科学是一个神经科学.

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