Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany.
Ann N Y Acad Sci. 2012 Aug;1266:18-27. doi: 10.1111/j.1749-6632.2012.06560.x.
Functional heterogeneity within stem and progenitor cells has been shown to influence cell fate decisions. Similarly, intracellular signaling activated by external stimuli is highly heterogeneous and its spatiotemporal activity is linked to future cell behavior. To quantify these heterogeneous states and link them to future cell fates, it is important to observe cell populations continuously with single cell resolution. Live cell imaging in combination with fluorescent biosensors for signaling activity serves as a powerful tool to study cellular and molecular heterogeneity and the long-term biological effects of signaling. Here, we describe these methodologies, their advantages over classical approaches, and we illustrate how they could be applied to improve our understanding of the importance of heterogeneous cellular and molecular responses to external signaling cues.
功能异质性在干细胞和祖细胞内已被证明会影响细胞命运决定。同样，外部刺激激活的细胞内信号也具有高度的异质性，其时空活性与未来的细胞行为相关。为了量化这些异质状态，并将其与未来的细胞命运联系起来，用单细胞分辨率连续观察细胞群体是很重要的。活细胞成像与用于信号活性的荧光生物传感器相结合，是研究细胞和分子异质性以及信号长期生物学效应的有力工具。在这里，我们描述了这些方法，以及它们相对于经典方法的优势，并举例说明了如何应用这些方法来提高我们对细胞和分子对外界信号的异质反应的重要性的理解。
