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Updated: Jun 13, 2025

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无偏见地对多功率景观进行分析,揭示了克隆命运偏差的空间调节器

Alek G Erickson, Sergey Isaev, Artem Artemov

bioRxiv : the preprint server for biology

|June 12, 2025

概括

这项研究揭示了在小鼠胚胎发生过程中细胞命运偏差的连续梯度,挑战了传统的树模型. 空间线索和基因网络动态地引导细胞分化,外部信号能够取代这些内在偏差.

科学领域:

发育生物学是发展生物学.
系统生物学系统生物学
遗传学是一个遗传学.

背景情况:

胚胎发生的传统模型侧重于细胞分化作为一棵树,忽视了多功率调制.
了解空间线索和基因调控网络的动态相互作用对于破译发育过程至关重要.

研究的目的:

描述胚胎在发育过程中的多功率格局.
研究血统规范和克隆命运偏差的机制.
探索外在信号在超越内在发育模式中的作用.

主要方法:

在小鼠胚胎中利用体内单细胞克隆血统追踪,从神经发育到妊娠中期.
使用机器学习工具根据共享的转录上下文对克隆进行分类.
执行了针对刺路径的马赛克组合扰动.

主要成果:

确定了一个连续的,胚胎范围的克隆命运偏差梯度,其中解剖位置和克隆组成是预测性的.
揭示了负责动态细胞命运的基因调节网络,由空间转录因子产生偏差.
证明了外在信号,如刺路径扰动,可以覆盖轴向模式和克隆命运偏差.

结论:

这项研究提出了一个新的胚胎发生的多功率景观模型,超越了传统的树木模型.
开发了一种有效的方法来剖析谱系规范机制.
这些发现对理解发育过程和推进干细胞工程有重大影响.

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