A nanobiosensor for dynamic single cell analysis during microvascular self-organization.
A nanobiosensor for dynamic single cell analysis during microvascular self-organization.
复制标题
用于微血管自组织过程中动态单细胞分析的纳米生物传感器。
作者：
Wang,S;Sun,J;Zhang,DD;Wong,PK
微血管网络的形成在再生医学和组织工程中发挥着重要作用。然而，由于缺乏绘制单细胞行为时空动态的有效工具，人们对动态形态发生过程背后的自组织机制知之甚少。通过建立单细胞纳米生物传感器和活细胞成像，我们对微血管自组织过程中的形态、位移和基因表达进行动态单细胞分析。动态单细胞分析揭示内皮细胞自组织成具有特殊表型的亚群，形成微血管网络，并确定了 Notch1-Dll4 信号传导参与调节细胞亚群。细胞表型与初始 Dll4 mRNA 表达水平相关，每个亚群都显示出独特的动态 Dll4 mRNA 表达谱。 Notch1-Dll4 信号传导的药理学扰动和 RNA 干扰可调节细胞亚群并改变微血管网络的形态。总而言之，纳米生物传感器实现了动态单细胞分析方法，强调了 Notch1-Dll4 信号在微血管自组织中的重要性。
The formation of microvascular networks plays essential roles in regenerative medicine and tissue engineering. Nevertheless, the self-organization mechanisms underlying the dynamic morphogenic process are poorly understood due to a paucity of effective tools for mapping the spatiotemporal dynamics of single cell behaviors. By establishing a single cell nanobiosensor along with live cell imaging, we perform dynamic single cell analysis of the morphology, displacement, and gene expression during microvascular self-organization. Dynamic single cell analysis reveals that endothelial cells self-organize into subpopulations with specialized phenotypes to form microvascular networks and identifies the involvement of Notch1-Dll4 signaling in regulating the cell subpopulations. The cell phenotype correlates with the initial Dll4 mRNA expression level and each subpopulation displays a unique dynamic Dll4 mRNA expression profile. Pharmacological perturbations and RNA interference of Notch1-Dll4 signaling modulate the cell subpopulations and modify the morphology of the microvascular network. Taken together, a nanobiosensor enables a dynamic single cell analysis approach underscoring the importance of Notch1-Dll4 signaling in microvascular self-organization.