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NGN3的振荡表达控制了人类胰腺内分泌分化的时间

Anzy Miller¹, Veronica Biga¹, Andrew Rowntree¹

¹Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.

Developmental cell

|June 26, 2025

概括

NEUROGENIN3 (NGN3) 蛋白质的振荡调节了胰腺内分泌细胞分化的时间. 数学建模和实验揭示了折叠变化检测,而不是表达水平,解码了这些NGN3动态.

科学领域:

细胞和分子生物学细胞和分子生物学
发展生物学发展生物学
系统生物学系统生物学

背景情况:

了解蛋白质表达动态是解读细胞分化机制的关键.
神经原蛋白3 (NGN3) 是胰腺内分泌发育的关键转录因子.

研究的目的:

研究NEUROGENIN3 (NGN3) 蛋白质表达的动态和解码机制.
了解NGN3蛋白振荡如何影响胰腺内分泌前体分化.

主要方法:

在人类诱导多能干细胞 (hiPSC) 衍生的内分泌前体中利用了一种内基 knockin 记者.
采用了蛋白质动态的单细胞分析,数学建模和实验验证.
研究了改变NGN3蛋白稳定性对分化时间的影响.

主要成果:

NGN3蛋白在hiPSC衍生的内分泌前体细胞中表现出~13小时的振荡,在分化为β类和前α细胞时停止.
增加的NGN3蛋白稳定性导致单个广泛的峰值,而不是振荡,导致早期内分泌分化.
通过不连贯的前循环 (IFFL) 模式,NGN3振荡是通过折叠变化检测 (FCD) 而不是表达水平来解码的.

结论:

NGN3蛋白的振荡动力学控制了胰腺内分泌分化的时间.
NGN3的振荡并不决定细胞的命运,而是调节分化速度.
不连贯的前循环 (IFFL) 模式解释了由NGN3动态驱动的正常和加速的分化过程.

关键词:

NGN3 NGN3 的时间.发展发展发展发展发展.表达的动态表达的动态.这是一个命运,命运的命运.折叠变换解码的解码方法人类干细胞分化分化振荡的振荡是如何发生的胰腺胰腺是什么时间表时间表转录因子的转录因子

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