Discovering New Progenitor Cell Populations through Lineage Tracing and In Vivo Imaging

Identification of progenitor cells that generate differentiated cell types during development, regeneration, and disease states is central to understanding the mechanisms governing such transitions. For more than a century, different lineage-tracing strategies have been developed, which helped disentangle the complex relationship between progenitor cells and their progenies. In this review, we discuss how lineage-tracing analyses have evolved alongside technological advances, and how this approach has contributed to the identification of progenitor cells in different contexts of cell differentiation. We also highlight a few examples in which lineage-tracing experiments have been instrumental for resolving long-standing debates and for identifying unexpected cellular origins. This discussion emphasizes how this century-old quest to delineate cellular lineage relationships is still active, and new discoveries are being made with the development of newer methodologies.