Collective dynamics in cell clusters

细胞簇中的集体动力学

• 批准号: 10194554
• 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/10194554
• 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.

项目总结 提出的研究将促进对细胞团动力学的机制理解。 具有稳定的胞间细胞质桥梁。这类多细胞系统被认为具有 在多细胞生物的出现过程中发挥了作用，并在当今发挥了关键作用 有机体。通过细胞质桥梁的细胞间运输产生了丰富的功能 显著的集体效应。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易处理的实验系统。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梁的细胞团：a 生殖系衍生的包含未来卵母细胞和15个哺育细胞的簇，以及体细胞簇 在包围生殖系簇的上皮细胞中。我们的研究确定了集体动力 在这两种组织类型中。首先，我们发现生殖系集群中的细胞在定义的组中生长 通过集群的连通性。AIM 1测试了这种增长模式依赖于 簇内的细胞间运输，反映内复制细胞的同步动力学 循环。其次，我们发现体细胞团表现出很强的克隆显性，a 通常被观察到，但对发育发育过程中的影响知之甚少。AIM 2测试 克隆优势度的出现是时空协调的结果 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研究 一类重要的多细胞系统的涌现动力学。鉴于无处不在的性质， 细胞团具有稳定的细胞质桥梁，我们的研究结果将产生广泛的影响。