Organism-wide spatiotemporal profiling of gene expression utilizing a X-CreERT2/Ai9 tracing system

This study utilizes a novel inducible X-CreERT2/Ai9 system to comprehensively delineate the spatial expression landscape of Fermt2, which encodes a key focal adhesion protein Kindlin-2, across organs in mice. We can confirm all known Kindlin-2-expressing cells and identify any previously unknown Kindlin-2-expressing cells and those that do not express Kindlin-2 in all tissues/organs in mice. We have developed this cost-effective, rapid, and high-fidelity system and implemented its first whole-organism application for comprehensive gene expression profiling. This work not only provides unprecedented insights into roles of Kindlin-2 in diverse physiologies and pathologies, but also establishes the inducible X-CreERT2/Ai9 system as a powerful paradigm-shifting platform for organism-wide pan-organ spatiotemporal expression profiling of any target genes encoding any proteins and micro-RNAs. By enabling high-resolution mapping of drug target expression, this system may lay critical groundwork for elucidating previously unknown adverse and beneficial effects of targeted therapies, offering transformative potential for precision medicine.