Illuminating Mammalian Cell Migration in Native Tissues at Subcellular and Molecular Resolution

Although cell migration has been extensively investigated using in vitro model systems, the mechanisms underlying mammalian cell migration in native tissue environments remain underexplored. Moreover, efforts to directly manipulate and visualize molecular regulators in live mammalian tissues have been scarce. In this article, we first review the current insights into various single-cell migration phenomena, including stem cell types, observed in mammalian tissues under homeostatic and pathophysiological conditions. Thereafter, we discuss intravital subcellular microscopy (ISMic) as a tool to unravel membrane remodeling mechanisms underlying cell migration in live animal tissues. Lastly, we emphasize the need for innovative microscopy and complementary advanced approaches to achieve a deeper fundamental understanding of cell migration modalities and their impact on mammalian tissue in homeostasis and pathophysiology.