Peláez Nicolás, Gavalda-Miralles Arnau, Wang Bao, Navarro Heliodoro Tejedor, Gudjonson Herman, Rebay Ilaria, Dinner Aaron R, Katsaggelos Aggelos K, Amaral Luís A N, Carthew Richard W
Department of Molecular Biosciences, Northwestern University, Evanston, United States.
Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, University Northwestern, Evanston, United States.
Elife. 2015 Nov 19;4:e08924. doi: 10.7554/eLife.08924.
Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells, with a rapid inductive phase and slow decay phase. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential. Consistent with this conclusion, perturbing Yan expression by varying gene dosage had no effect on cell fate transitions. However, we observed that as cells transited to differentiation, Yan expression became highly heterogeneous and this heterogeneity was transient. Signals received via the EGF Receptor were necessary for the transience in Yan noise since genetic loss caused sustained noise. Since these signals are essential for eye cells to differentiate, we suggest that dynamic heterogeneity of Yan is a necessary element of the transition process, and cell states are stabilized through noise reduction.
Yan是一种ETS结构域转录因子，负责将果蝇眼细胞维持在多能状态。Yan处于一个调控网络的核心，该网络决定了细胞从多能性转变为几种分化谱系之一的时间和位置。使用Yan表达的荧光报告基因，我们观察到Yan在多能细胞中的双相分布，包括快速诱导期和缓慢衰退期。向各种分化状态的转变发生在这个动态过程中，这表明Yan的表达水平并不能强烈地决定细胞潜能。与这一结论一致，通过改变基因剂量来干扰Yan的表达对细胞命运转变没有影响。然而，我们观察到，随着细胞向分化转变，Yan的表达变得高度异质性，并且这种异质性是短暂的。通过表皮生长因子受体接收的信号对于Yan噪声的短暂性是必要的，因为基因缺失会导致持续的噪声。由于这些信号对于眼细胞分化至关重要，我们认为Yan的动态异质性是转变过程的必要元素，并且细胞状态通过噪声降低得以稳定。
