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在小鼠胚胎干细胞中识别和功能评估Dax1的替代拼接变体

Jiaqi Wang^1,2, Yi Huang³, Chen Zhang¹

¹Laboratory of Stem Cell and Developmental Biology, Department of Histology and Embryology, College of Basic Medical Science, Army Medical University, Chongqing, China.

Stem cells and development

|June 1, 2023

概括

研究人员在小鼠胚胎干细胞 (ESC) 中发现了18种新的Dax1 (X染色体基因-1上先天产生的剂量敏感性性别逆转-上腺缩) 拼接变异. 这些变体表现出不同的表达模式和细胞局部化,影响多能性调节.

科学领域:

发展生物学发展生物学
干细胞生物学干细胞生物学
分子遗传学分子遗传学

背景情况:

达克斯1 (Nr0b1) 对于维持小鼠胚胎干细胞 (ESCs) 的多能性至关重要.
转录因子的替代拼接可以显著影响ESC多能性和自我更新.
在老鼠ESC中Dax1拼接变体以前没有被识别或描述.

研究的目的:

在小鼠ESC中识别和描述新的Dax1拼接变体.
调查这些变体的表达模式和亚细胞局部化.
确定Dax1变异对ESC自我更新和基因调节的功能影响.

主要方法:

转录的生物信息分析以识别新的Dax1变种.
鉴定变体和已知的Dax1.1的蛋白质结构的比较分析.
对表达模式和单细胞转录异质性的定量分析.
编码蛋白质的亚细胞局部化研究.
功能性测试以评估对 Gata6 转录和 Dax1-472 活性的影响.

主要成果:

确定了18个新的Dax1转录,具有假定的蛋白质编码特性.
在小鼠ESC中,新型Dax1异型与Dax1-472共同转录,显示出单细胞转录异质性.
编码的蛋白质表现出差异性的亚细胞局部化.
达克斯1-404抑制了Gata6转录,并在功能上替代了达克斯1-472.
达克斯1-38和达克斯1-225部分对抗达克斯1-472的转录抑制.

结论:

在小鼠ESC中实现了Dax1拼接变体的全面表征.
达克斯1变种显示出多样化的表达,本地化和功能性质.
这些变体在ESC自我更新网络中产生复杂的监管效应,为Dax1的功能增加了复杂性.

关键词:

达克斯 (Dax) 是一个名为达克斯的世界.另一个替代拼接变种.胚胎干细胞是一种胚胎干细胞.它是自我更新的.转录抑制剂转录抑制剂

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