Collective dynamics in cell clusters

细胞簇中的集体动力学

• 批准号: 10448474
• 负责人: Stanislav Y. Shvartsman
• 金额: $ 31.52万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10448474
• 关键词: Biology; Biophysics; Cell Cycle; Cell Cycle Progression; Cells; Computer Models; Defect; Development; Drosophila genus; Epithelial; Feedback; Future; Gametogenesis; Growth; Image; Mitotic Cell Cycle; Modeling; Nature; Nurses; Oocytes; Oogenesis; Organelles; Organism; Organogenesis; Pattern; Play; Process; Research; Role; Somatic Cell; System; Testing; Tissues; Trees; Work; cell growth; cell type; dynamic system; experimental study; insight; predictive modeling; public health relevance; spatiotemporal; theories; tool

PROJECT SUMMARY The proposed research will advance the mechanistic understanding of dynamics in cell clusters with stable intercellular cytoplasmic bridges. This class of multicellular systems is thought to have played a role during the emergence of multicellularity and serves critical functions in present day organisms. Intercellular transport through cytoplasmic bridges gives rise to a wealth of functionally significant collective effects. One key obstacle in understanding the origins of these effects is the current lack of tractable experimental systems that can be studied quantitatively. Our research will use Drosophila oogenesis, an experimental system that provides unmatched opportunities for quantitative studies. This system relies on two types of cell clusters with cytoplasmic bridges: a germline-derived cluster containing the future oocyte and 15 nurse cells, and somatic cell clusters in the epithelium that envelops the germline cluster. Our research identified collective dynamics in both tissue types. First, we discovered that cells in the germline cluster grow in groups defined by the cluster's connectivity. Aim 1 tests the hypothesis that this growth pattern depends on intercellular transport within the cluster and reflects synchronized dynamics of endoreplication cell cycles. Second, we showed that somatic cell clusters display strong clonal dominance, a commonly observed, yet poorly understood effect during developmental growth. Aim 2 tests the hypothesis that clonal dominance emerges as a consequence of spatiotemporal coordination of mitotic cell cycles. Our work uses live imaging and computational modeling to investigate emergent dynamics in an important class of multicellular systems. Given the ubiquitous nature of cell clusters with stable cytoplasmic bridges, results of our studies will have broad impact.

项目概要 拟议的研究将促进对细胞簇动力学的机械理解 具有稳定的细胞间胞质桥。此类多细胞系统被认为具有 在多细胞出现期间发挥了作用，并在当今发挥着重要作用 有机体。通过细胞质桥的细胞间运输产生了丰富的功能 显着的集体效应。理解这些效应的起源的一个主要障碍是 目前缺乏可进行定量研究的易于处理的实验系统。我们的研究 将使用果蝇卵子发生，这是一个实验系统，为 定量研究。该系统依赖于两种类型的具有细胞质桥的细胞簇： 包含未来卵母细胞和 15 个护理细胞的种系衍生簇，以及体细胞簇 在包围种系簇的上皮细胞中。我们的研究确定了集体动力 在两种组织类型中。首先，我们发现种系簇中的细胞按定义的组生长 通过集群的连接性。目标 1 检验这一增长模式取决于的假设 簇内的细胞间运输并反映内复制细胞的同步动态 循环。其次，我们发现体细胞簇表现出很强的克隆优势， 在发育生长过程中普遍观察到但知之甚少的效应。目标 2 测试 克隆优势是由于时空协调而出现的假设 有丝分裂细胞周期。我们的工作使用实时成像和计算模型来研究 一类重要的多细胞系统中的涌现动力学。鉴于无处不在的性质 细胞簇具有稳定的细胞质桥，我们的研究结果将产生广泛的影响。