Diegmiller Rocky, Nunley Hayden, Shvartsman Stanislav Y, Imran Alsous Jasmin
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Interface Focus. 2022 Jun 10;12(4):20210082. doi: 10.1098/rsfs.2021.0082. eCollection 2022 Aug 6.
Small cell clusters exhibit numerous phenomena typically associated with complex systems, such as division of labour and programmed cell death. A conserved class of such clusters occurs during oogenesis in the form of germline cysts that give rise to oocytes. Germline cysts form through cell divisions with incomplete cytokinesis, leaving cells intimately connected through intercellular bridges that facilitate cyst generation, cell fate determination and collective growth dynamics. Using the well-characterized female germline cyst as a foundation, we present mathematical models rooted in the dynamics of cell cycle proteins and their interactions to explain the generation of germline cell lineage trees (CLTs) and highlight the diversity of observed CLT sizes and topologies across species. We analyse competing models of symmetry breaking in CLTs to rationalize the observed dynamics and robustness of oocyte fate specification, and highlight remaining gaps in knowledge. We also explore how CLT topology affects cell cycle dynamics and synchronization and highlight mechanisms of intercellular coupling that underlie the observed collective growth patterns during oogenesis. Throughout, we point to similarities across organisms that warrant further investigation and comment on the extent to which experimental and theoretical findings made in model systems extend to other species.
小细胞簇表现出许多通常与复杂系统相关的现象，如分工和程序性细胞死亡。一类保守的此类细胞簇在卵子发生过程中以生殖系囊肿的形式出现，这些囊肿会产生卵母细胞。生殖系囊肿通过不完全胞质分裂的细胞分裂形成，细胞通过细胞间桥紧密相连，这些桥促进囊肿的形成、细胞命运的决定和集体生长动态。以特征明确的雌性生殖系囊肿为基础，我们提出了基于细胞周期蛋白动力学及其相互作用的数学模型，以解释生殖系细胞谱系树（CLT）的产生，并突出观察到的不同物种CLT大小和拓扑结构的多样性。我们分析了CLT中对称破缺的竞争模型，以合理化观察到的卵母细胞命运指定的动态和稳健性，并突出知识上的剩余差距。我们还探讨了CLT拓扑结构如何影响细胞周期动态和同步，并突出了在卵子发生过程中观察到的集体生长模式背后的细胞间耦合机制。在整个过程中，我们指出了不同生物体之间的相似性，值得进一步研究，并评论了模型系统中的实验和理论发现扩展到其他物种的程度。
