利用邻近细胞遗传学技术揭示哺乳动物体内细胞间相互作用

Intercellular Genetics Reveals Cell-Cell Interactions in Mammals

细胞与细胞之间的交流和相互作用是多细胞生物的一项基本特征,解析细胞之间的相互作用对于深入了解多种生物学过程及其调控机制具有重要意义。但是目前领域内缺乏研究体内细胞互作的技术手段。该团队将人工合成Notch信号通路(synNotch)技术与传统遗传学手段相结合,建立了邻近细胞遗传学技术,用于监测细胞间相互作用并永久示踪接触过的细胞。通过构建表达synNotch通路的遗传工具小鼠,该团队在两种不同类型细胞中分别表达synNotch配体蛋白和受体蛋白,当相邻细胞配体和受体特异结合后,synNotch信号通路被激活从而开启下游报告基因原件的表达,实现遗传标记和永久示踪受体细胞。该团队利用邻近细胞遗传学技术揭示了心脏中心肌细胞和内皮细胞,以及肿瘤中肿瘤细胞和内皮细胞之间的动态相互作用。邻近细胞遗传学技术可以解决众多与细胞相互作用相关的重要科学问题,有助于开拓新的细胞互作研究方向。

Cell-cell communication and interactions are essential for multicellular organisms.Monitoring and elucidation of their interactions is fundamental to understanding the diverse biological processes.However,in vivo genetic monitoring of cell-cell interactions remains challenging to date.In this study,this group developed a proximal cell genetics,combining synNotch with traditional genetic approaches,to monitor in vivo cell-cell interactions,as well as to permanently trace their contact histories.This group generated knock-in mice that expressed synNotch elements,where an artificial Notch ligand was expressed in one cell type(sender cells)and an artificial receptor in another cell type(receiver cells).The specific binding of ligand and receptor between two contacting cells activates synNotch pathway,and initiates the expression of reporter gene in receptor cells,thus enabling genetic labelling and lineage tracing of the receptor cells.Using the proximal cell genetics,this group revealed the dynamic interactions between endothelial cells with cardiomyocytes or tumor cells.This proximal cell genetic approach could be widely applied to understand scientific questions involved with cell-cell interaction,opening new window for study cell-cell communication.