Xiong Ruiqi, Su Yang, Yao Mengchao, Liu Zefei, Lu Jie, Chen Yong-Cong, Ao Ping
Shanghai Center for Quantitative Life Sciences & Department of Physics, Shanghai University, Shanghai 200444, China.
College of Mechanical Engineering, Beijing Institute of Technology at Zhuhai Campus, Zhuhai 519088, China.
Genetics. 2025 Jul 9;230(3). doi: 10.1093/genetics/iyaf095.
The nematode Caenorhabditis elegans exhibits an invariant cell lineage during its development, where the gene-molecular network that regulates the development is crucial for the biological process. While there are many molecular cell atlases describing the phenomena and key molecules involved in cell transformation, the underlying mechanisms from a systems biology perspective have received less attention. Based on an endogenous molecular-cellular theory that relates the molecular mechanisms to biological phenotypes, we constructed a model of the core endogenous network to describe the early stages of embryonic development of the C. elegans. Different cell types and intermediate cell states during development from zygotes to founder cells correspond to the steady states of the network as a nonlinear stochastic dynamical system. Connections between steady states form a topological landscape that encompasses known developmental lineage trajectories. By regulating the expression of agents in the network, we quantitatively simulated the effects of the Wnt and Notch signaling pathway on cell fate transitions and predicted the possible trajectories of transdifferentiation of the AB cell across the lineage. The success of the current study may help advance our understanding of the fundamental principles of developmental biology and cell fate determination, offering an effective tool for the quantitative analysis of cellular processes.
线虫秀丽隐杆线虫在其发育过程中表现出不变的细胞谱系，其中调节发育的基因 - 分子网络对生物过程至关重要。虽然有许多分子细胞图谱描述了细胞转化中涉及的现象和关键分子，但从系统生物学角度来看的潜在机制却较少受到关注。基于一种将分子机制与生物表型相关联的内源性分子 - 细胞理论，我们构建了一个核心内源性网络模型来描述秀丽隐杆线虫胚胎发育的早期阶段。从受精卵到奠基细胞发育过程中的不同细胞类型和中间细胞状态对应于作为非线性随机动力系统的网络的稳态。稳态之间的连接形成了一个拓扑景观，其中包含已知的发育谱系轨迹。通过调节网络中因子的表达，我们定量模拟了Wnt和Notch信号通路对细胞命运转变的影响，并预测了AB细胞跨谱系转分化的可能轨迹。当前研究的成功可能有助于推进我们对发育生物学和细胞命运决定基本原理的理解，为细胞过程的定量分析提供一种有效的工具。
