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.

项目摘要 拟议的研究将提高对细胞簇动力学的机械理解 具有稳定的细胞间细胞质桥。这类多细胞系统被认为具有 在多细胞的出现中起着作用，并在当今发挥关键功能 有机体。通过细胞质桥的细胞间运输会在功能上增加 重大的集体效应。理解这些影响的起源的一个关键障碍是 目前缺乏可定量研究的可拖动实验系统。我们的研究 将使用果蝇卵子发生，这是一种实验系统，为无与伦比的机会提供了无与伦比的机会 定量研究。该系统依赖于具有细胞质桥的两种类型的细胞簇：A 含有未来卵母细胞和15个护士细胞的种系衍生的簇以及体细胞簇 在包裹种系簇的上皮中。我们的研究确定了集体动态 在两种组织中。首先，我们发现种系簇中的细胞成群的定义生长 通过集群的连接。 AIM 1检验了这种增长模式取决于的假设 群集内的细胞间传输，反映了内磁细胞的同步动力学 周期。其次，我们表明体细胞簇显示出强的克隆优势，一个 通常观察到，但在发育增长过程中的影响很少。 AIM 2测试 假设克隆统治是由于时空协调而出现的 有丝分裂细胞周期。我们的工作使用实时成像和计算建模来调查 一类重要的多细胞系统中的新兴动力学。鉴于无处不在的性质 具有稳定的细胞质桥的细胞簇，我们的研究结果将产生广泛的影响。