School of Engineering and Applied Sciences, Harvard University, Wyss Institute for Biologically Inspired Engineering, USA.
Integr Biol (Camb). 2012 Mar;4(3):292-300. doi: 10.1039/c2ib00057a. Epub 2012 Feb 9.
Many biological processes, including angiogenesis, involve intercellular feedback and temporal coordination, but inference of these relations is often drowned in low sample sizes or noisy population data. To address this issue, a methodology was developed to statistically study spatial lateral inhibition and temporal synchronization in one specific biological process, endothelial sprouting mediated by Notch signaling. Notch plays an essential role in the development of organized vasculature, but the effects of Notch on the temporal characteristics of angiogenesis are not well understood. Results from this study showed that Notch lateral inhibition operates at distances less than 31 μm. Furthermore, combining time lapse microscopy with an intraclass correlation model typically used to analyze family data showed intrinsic temporal synchronization among endothelial sprouts originating from the same microcarrier. Such synchronization was reduced with Notch inhibitors, but was enhanced with the addition of Notch ligands. These results indicate that Notch plays a critical role in the temporal regulation of angiogenesis, as well as spatial control, and this method of analysis will be of significant utility in studies of a variety of other biological processes.
许多生物过程，包括血管生成，都涉及细胞间的反馈和时间协调，但这些关系的推断常常被淹没在低样本量或嘈杂的群体数据中。为了解决这个问题，开发了一种方法来统计研究 Notch 信号介导的内皮发芽这一特定生物学过程中的空间横向抑制和时间同步。Notch 在有组织的脉管系统发育中起着至关重要的作用，但 Notch 对血管生成的时间特征的影响还不是很清楚。本研究的结果表明，Notch 横向抑制作用在小于 31μm 的距离上发生。此外，将延时显微镜与通常用于分析家族数据的组内相关模型相结合，显示了源自同一微载体的内皮芽之间固有的时间同步性。用 Notch 抑制剂处理后，这种同步性降低，但添加 Notch 配体后增强。这些结果表明，Notch 在血管生成的时间调节中以及空间控制中起着关键作用，这种分析方法将在其他各种生物学过程的研究中具有重要的应用价值。
