Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning.
Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning.
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DOI：
10.1016/j.devcel.2018.09.023
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发表时间：
2018-11-19
影响因子：
11.8
通讯作者：
Thompson CRL
中科院分区：
文献类型：
--
作者：
Gruenheit N;Parkinson K;Brimson CA;Kuwana S;Johnson EJ;Nagayama K;Llewellyn J;Salvidge WM;Stewart B;Keller T;van Zon W;Cotter SL;Thompson CRL
细胞-细胞异质性可以促进胚胎发育过程中的谱系选择，因为它使细胞对分化信号做出反应。然而，非常少的是已知的异质性的起源或是否可以控制内在和外在的变化，以产生可重复的细胞类型比例在体内看到。在这里，我们使用实验和建模D. discoideum证明，群体水平的细胞周期异质性可以优化，以产生强大的细胞命运比例。首先，细胞周期的位置是定量的分化诱导信号的反应。其次，细胞周期长度的内在变化确保了细胞在多细胞发育开始时在整个细胞周期中随机分布。最后，最佳细胞周期异质性的外在扰动被全局信号反应性的补偿性变化所缓冲。因此，这些研究阐明了细胞-细胞异质性优化和在发育中产生稳健和可重复的命运选择的关键调控原则。细胞周期位置影响对分化诱导信号的反应性细胞周期长度的变化确保细胞分布在不同的周期阶段细胞周期动力学的扰动被信号反应性的变化所缓冲。发现细胞周期位置的异质性促进发育过程中的对称性破坏，因为它有助于细胞对不同的分化线索做出反应。通过信号响应的变化进行缓冲确保了该系统对细胞周期动力学的扰动具有鲁棒性。这说明了如何优化异质性以促进开发。
Cell-cell heterogeneity can facilitate lineage choice during embryonic development because it primes cells to respond to differentiation cues. However, remarkably little is known about the origin of heterogeneity or whether intrinsic and extrinsic variation can be controlled to generate reproducible cell type proportioning seen in vivo. Here, we use experimentation and modeling in D. discoideum to demonstrate that population-level cell cycle heterogeneity can be optimized to generate robust cell fate proportioning. First, cell cycle position is quantitatively linked to responsiveness to differentiation-inducing signals. Second, intrinsic variation in cell cycle length ensures cells are randomly distributed throughout the cell cycle at the onset of multicellular development. Finally, extrinsic perturbation of optimal cell cycle heterogeneity is buffered by compensatory changes in global signal responsiveness. These studies thus illustrate key regulatory principles underlying cell-cell heterogeneity optimization and the generation of robust and reproducible fate choice in development. Dictyostelium cells break symmetry in a stochastic salt and pepper fashion Cell cycle position affects responsiveness to differentiation inducing signals Cell cycle length variation ensures cells are distributed in different cycle phases Perturbation of cell cycle dynamics is buffered by changes in signal responsiveness Gruenheit et al. find cell cycle position heterogeneity promotes symmetry breaking during development as it helps cells respond to different differentiation cues. Buffering by changes in signal responses ensures this system is robust to perturbation of cell cycle dynamics. This illustrates how heterogeneity can be optimized to facilitate development.
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影响因子：
56.9
作者：
GOMER, RH;FIRTEL, RA
通讯作者：
FIRTEL, RA
影响因子：
56.9
作者：
Maamar, Hedia;Raj, Arjun;Dubnau, David
通讯作者：
Dubnau, David
DOI：
10.1073/pnas.1408638111
发表时间：
2014-07-01
影响因子：
11.1
作者：
Li, Victor C.;Kirschner, Marc W.
通讯作者：
Kirschner, Marc W.
影响因子：
2.7
作者：
KONIJN, TM;RAPER, KB
通讯作者：
RAPER, KB
影响因子：
4
作者：
Parkinson, Katie;Bolourani, Parvin;Thompson, Christopher R. L.
通讯作者：
Thompson, Christopher R. L.