Data-Driven Models Reveal Mutant Cell Behaviors Important for Myxobacterial Aggregation
Data-Driven Models Reveal Mutant Cell Behaviors Important for Myxobacterial Aggregation
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数据驱动模型揭示突变细胞行为对粘细菌聚集很重要
DOI：
10.1128/msystems.00518-20
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发表时间：
2020
期刊：
影响因子：
6.4
通讯作者：
Rust, Michael
中科院分区：
文献类型：
--
作者：
Zhang, Zhaoyang;Cotter, Christopher R.;Lyu, Zhe;Shimkets, Lawrence J.;Igoshin, Oleg A.;Rust, Michael
单个突变经常改变细胞行为的几个方面，但很少揭示特定的统计学显著变化是否具有生物学意义。为了确定哪些行为变化对多细胞自组织最重要，我们设计了一种新的方法，使用粘球菌作为模型系统。在发育过程中，粘细菌协调它们的运动，聚集成充满孢子的子实体。我们研究如何聚集恢复在两个突变体，csgAandpilC，不能聚集，除非与野生型（WT）细胞混合。为此，我们使用细胞跟踪来跟踪荧光标记细胞的运动，并结合数据驱动的基于代理的建模。结果表明，就像WT细胞一样，两种突变体都使它们的运动偏向于聚集体，并降低聚集体内部的运动性。然而，突变体行为的几个方面仍然没有得到WT的纠正，这表明WT行为的完美重建是不必要的。事实上，错误行为之间的协同作用可以使聚集鲁棒。重要信息自组织成空间模式在许多多细胞现象中是显而易见的。即使对于研究得最好的系统，我们剖析驱动协调细胞运动的机制的能力也是有限的。虽然遗传学方法可以识别干扰多细胞模式的突变，但信号线索的多样性与个体细胞行为的显著异质性相结合，阻碍了我们将基因与表型机械连接的能力。突变株行为的微小差异可能无关紧要，有时可能导致出现模式的巨大差异。在这里，我们调查救援的多细胞聚集在两个突变株粘球菌与野生型细胞混合。结果表明，仔细量化细胞行为与数据驱动的建模相结合，可以识别负责细胞聚集的特定运动特征，从而揭示重要的协同作用和补偿机制。值得注意的是，突变细胞不需要精确地重建野生型行为来实现完全聚集。
Single mutations frequently alter several aspects of cell behavior but rarely reveal whether a particular statistically significant change is biologically significant. To determine which behavioral changes are most important for multicellular self-organization, we devised a new methodology using Myxococcus xanthus as a model system. During development, myxobacteria coordinate their movement to aggregate into spore-filled fruiting bodies. We investigate how aggregation is restored in two mutants,csgAandpilC, that cannot aggregate unless mixed with wild-type (WT) cells. To this end, we use cell tracking to follow the movement of fluorescently labeled cells in combination with data-driven agent-based modeling. The results indicate that just like WT cells, both mutants bias their movement toward aggregates and reduce motility inside aggregates. However, several aspects of mutant behavior remain uncorrected by WT, demonstrating that perfect recreation of WT behavior is unnecessary. In fact, synergies between errant behaviors can make aggregation robust.IMPORTANCESelf-organization into spatial patterns is evident in many multicellular phenomena. Even for the best-studied systems, our ability to dissect the mechanisms driving coordinated cell movement is limited. While genetic approaches can identify mutations perturbing multicellular patterns, the diverse nature of the signaling cues coupled to significant heterogeneity of individual cell behavior impedes our ability to mechanistically connect genes with phenotype. Small differences in the behaviors of mutant strains could be irrelevant or could sometimes lead to large differences in the emergent patterns. Here, we investigate rescue of multicellular aggregation in two mutant strains of Myxococcus xanthus mixed with wild-type cells. The results demonstrate how careful quantification of cell behavior coupled to data-driven modeling can identify specific motility features responsible for cell aggregation and thereby reveal important synergies and compensatory mechanisms. Notably, mutant cells do not need to precisely recreate wild-type behaviors to achieve complete aggregation.
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DOI：
10.1103/physreve.70.041911
发表时间：
2004
期刊：
Physical review. E, Statistical, nonlinear, and soft matter physics
影响因子：
--
作者：
O. Igoshin;J. Neu;G. Oster
通讯作者：
G. Oster
DOI：
10.1073/pnas.96.9.5031
发表时间：
1999-04-27
影响因子：
11.1
作者：
Jelsbak, L;Sogaard-Andersen, L
通讯作者：
Sogaard-Andersen, L
影响因子：
3.6
作者：
Konovalova, Anna;Wegener-Feldbruegge, Sigrun;Sogaard-Andersen, Lotte
通讯作者：
Sogaard-Andersen, Lotte
影响因子：
2.7
作者：
HAGEN, DC;BRETSCHER, AP;KAISER, D
通讯作者：
KAISER, D
DOI：
--
发表时间：
2014
期刊：
影响因子：
--
作者：
S. Thutupalli;Mingzhai Sun;F. Bunyak;K. Palaniappan;J. Shaevitz
通讯作者：
J. Shaevitz