A hybrid model connecting regulatory interactions with stem cell divisions in the root.

Lisa Van den Broeck, Ryan J Spurney, Adam P Fisher, Michael Schwartz, Natalie M Clark, Thomas T Nguyen, Imani Madison, Mariah Gobble, Terri Long, Rosangela Sozzani
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引用次数: 5

Abstract

Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.

Abstract Image

Abstract Image

Abstract Image

一个连接调控相互作用与根中干细胞分裂的混合模型。
干细胞在一个器官内产生完整的细胞。维持干细胞的身份和协调调节干细胞的分裂是干细胞正常发育的关键。在植物中,移动蛋白,如wuschell相关的HOMEOBOX 5 (WOX5)和SHORTROOT (SHR),调节根干细胞生态位的分裂。然而,这些蛋白质如何协调作用以建立系统行为尚不清楚。我们提出了WOX5在皮层内胚层初始(CEI)中的非细胞自主作用,并确定了一个调节因子ANGUSTIFOLIA (AN3)/ grf - interaction FACTOR 1,该因子协调CEI分裂。在此,我们通过一个多尺度混合模型,将常微分方程(ode)和基于智能体的建模相结合,证明了静止中心(QC)和CEI划分具有不同的动态特性。具体来说,通过结合连续模型来描述调控网络和基于agent的规则,我们模拟了系统行为,这使我们预测了SHR、稻草人、WOX5、AN3和CYCLIND6;1的细胞类型特异性表达动态,并通过实验验证了CEI细胞分裂。最后,我们的结果表明CEI和QC部门之间存在相互依赖关系。
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