标题： 在协调组织发育模型中结合随机基因表达、信号介导的细胞间相互作用和调控的细胞增殖 显示英文标题

标题： Incorporating stochastic gene expression, signaling-mediated intercellular interactions, and regulated cell proliferation in models of coordinated tissue development

摘要： 构建组织发育的定量和预测模型需要考虑复杂的、随机的基因表达动态，其通过细胞间相互作用的调控以及细胞增殖。将所有这些过程纳入一个实用的数学框架需要复杂的表达式，这些表达式难以解释和应用。我们构建了一个简单的理论，该理论结合了细胞内随机的基因表达动态、影响这些动态并介导细胞间相互作用的信号化学物质，以及细胞增殖及其伴随的分化。细胞状态（遗传和表观遗传）由一个Waddington向量场描述，该向量场允许非梯度动力学（循环、熵产生、详细平衡的丧失），这在Waddington势能景观表示的基因表达动态中是被排除的。我们定义了一个表观遗传适应度景观，用于描述不同细胞类型的增殖，并阐明该适应度景观与Waddington向量场之间的关系。我们通过分析两个模型系统来说明我们框架的适用性：一个相互作用的两基因分化过程和一个受涡虫启发的时空生物体模型。 显示英文摘要

摘要： Formulating quantitative and predictive models for tissue development requires consideration of the complex, stochastic gene expression dynamics, its regulation via cell-to-cell interactions, and cell proliferation. Including all of these processes into a practical mathematical framework requires complex expressions that are difficult to interpret and apply. We construct a simple theory that incorporates intracellular stochastic gene expression dynamics, signaling chemicals that influence these dynamics and mediate cell-cell interactions, and cell proliferation and its accompanying differentiation. Cellular states (genetic and epigenetic) are described by a Waddington vector field that allows for non-gradient dynamics (cycles, entropy production, loss of detailed balance) which is precluded in Waddington potential landscape representations of gene expression dynamics. We define an epigenetic fitness landscape that describes the proliferation of different cell types, and elucidate how this fitness landscape is related to Waddington's vector field. We illustrate the applicability of our framework by analyzing two model systems: an interacting two-gene differentiation process and a spatiotemporal organism model inspired by planaria.