Intercellular Genetics Reveals Cell-Cell Interactions in Mammals
ZHANG Shaohua, ZHAO Huan, ZHOU Bin*
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.
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