Leiden Institute of Physics, Leiden University, Leiden, The Netherlands.
Biochem Soc Trans. 2021 Dec 17;49(6):2509-2525. doi: 10.1042/BST20210135.
On its path from a fertilized egg to one of the many cell types in a multicellular organism, a cell turns the blank canvas of its early embryonic state into a molecular profile fine-tuned to achieve a vital organismal function. This remarkable transformation emerges from the interplay between dynamically changing external signals, the cell's internal, variable state, and tremendously complex molecular machinery; we are only beginning to understand. Recently developed single-cell omics techniques have started to provide an unprecedented, comprehensive view of the molecular changes during cell-type specification and promise to reveal the underlying gene regulatory mechanism. The exponentially increasing amount of quantitative molecular data being created at the moment is slated to inform predictive, mathematical models. Such models can suggest novel ways to manipulate cell types experimentally, which has important biomedical applications. This review is meant to give the reader a starting point to participate in this exciting phase of molecular developmental biology. We first introduce some of the principal molecular players involved in cell-type specification and discuss the important organizing ability of biomolecular condensates, which has been discovered recently. We then review some of the most important single-cell omics methods and relevant findings they produced. We devote special attention to the dynamics of the molecular changes and discuss methods to measure them, most importantly lineage tracing. Finally, we introduce a conceptual framework that connects all molecular agents in a mathematical model and helps us make sense of the experimental data.
从受精卵到多细胞生物体的众多细胞类型之一，细胞将其早期胚胎状态的空白画布转变为精细调整的分子特征，以实现重要的生物体功能。这种显著的转变源于动态变化的外部信号、细胞内部可变状态和极其复杂的分子机制之间的相互作用；我们才刚刚开始了解。最近开发的单细胞组学技术开始提供细胞类型特化过程中分子变化的前所未有的全面视图，并有望揭示潜在的基因调控机制。目前正在创建的定量分子数据呈指数级增长，预计将为预测性、数学模型提供信息。这些模型可以提出实验操纵细胞类型的新方法，这在生物医学中有重要的应用。这篇综述旨在为读者提供一个起点，以参与分子发育生物学的这一令人兴奋的阶段。我们首先介绍一些参与细胞类型特化的主要分子参与者，并讨论最近发现的生物分子凝聚物的重要组织能力。然后，我们回顾一些最重要的单细胞组学方法及其产生的相关发现。我们特别关注分子变化的动态，并讨论测量它们的方法，最重要的是谱系追踪。最后，我们引入了一个概念框架，将数学模型中的所有分子因子连接起来，并帮助我们理解实验数据。
