Dual recombinases-based genetic lineage tracing for stem cell research with enhanced precision

Stem cell research has become a hot topic in biology, as the understanding of stem cell biology can provide new insights for both regenerative medicine and clinical treatment of diseases. Accurately deciphering the fate of stem cells is the basis for understanding the mechanism and function of stem cells during tissue repair and regeneration. Cre-loxP-mediated recombination has been widely applied in fate mapping of stem cells for many years. However, nonspecific labeling by conventional cell lineage tracing strategies has led to discrepancies or even controversies in multiple fields. Recently, dual recombinase-mediated lineage tracing strategies have been developed to improve both the resolution and precision of stem cell fate mapping. These new genetic strategies also expand the application of lineage tracing in studying cell origin and fate. Here, we review cell lineage tracing methods, especially dual genetic approaches, and then provide examples to describe how they are used to study stem cell fate plasticity and function in vivo.