Analyzing cell migration history in vivo using fluorescent fibrillar collagen trails

Cell migration is a critical process in development, homeostasis, and disease. While cell migration in vitro is well investigated, much less is known about migration deep within tissues, largely due to limitations associated with deep cell imaging in tissues. In this study, we investigated cell migration history in vivo by developing a strategy based on recording cell trails formed by fusion of fluorescent protein and collagen secreted by migrating cells. By engineering different cell lines to express either fluorescent protein-fused Col1a1 or Col1a2 we identified trails formed in normal mouse tissues as well as primary tumors and metastatic organ sites. Analyses of the trail patterns revealed the paths taken by migrating cells and regions that suggest group trails, including trails along vascular adventitia. These results demonstrate that cell migration history can be traced in mouse models through postmortem analysis of normal and cancerous tissues. To unlock the secrets of deep tissue cell migration, the authors have engineered a new strategy to trace in vivo cell paths by capturing fluorescent collagen trails left behind by moving cells in order to make cell migration history mapping possible.