Dual genetic approaches for deciphering cell fate plasticity in vivo: more than double

Unravelling stem cell fate plasticity is significant for understanding pathophysiology and exploring new therapeutic targets. The Cre-loxP genetic system is commonly used for cell lineage tracing. However, this conventional approach has limitations that have led to controversies in multiple fields. In recent years, there has been growing interest in a dual genetic approach based on Cre-loxP and another orthogonal recombinase. The dual genetic approach permits cell tracking at a significantly higher resolution and enables a more precise method for gene manipulation and cell fate control. Here, we review the recent progress in dual genetic approaches and highlight emerging work to demonstrate how the application of these approaches advances our understanding of stem cell fate plasticity for tissue repair and regeneration.