Bon-Kyoung Koo

Center for Genome Engineering, Institute for Basic Science, Korea

Biodiversity reflects evolutionary strategies for survival and adaptation. Yet even as next-generation sequencing opens genomic study to diverse species, cell-based  comparative  biology  still  lags  without  a  unified  experimental platform. Here, we established a cross-species“organoid zoo”of adult stem cell–derived  intestinal  organoids  from  26  vertebrate  species,  comprising mainly mammals and a few avians, including rodents, bats, pets, farm animals, and experimental models such as mice, rats, ferrets, minipigs, and primates. These organoids can be robustly maintained in a standardized, commercially

available medium, enabling systematic cross-species analysis. We demonstrate the platform’s versatility through single-cell RNA sequencing, biobanking, regeneration assays, viral infection modeling, genome editing,  and  drug  screening  across  nearly  all  species  represented.  Our  comparative transcriptomics identified  Solute  Carrier  Family  12  member  2  (Slc12a2)  and  Cyclin-Dependent  Kinase  6  (Cdk6)  as conserved intestinal stem cell markers. Functionally, spiny mouse organoids exhibit enhanced regeneration driven by a YAP-enhanced stem cell population, while cross-species infection assays with eight different viruses revealed diverse viral susceptibilities among mammalian and avian lineages. The organoid zoo provides a scalable and comparative framework to study regeneration, disease, and fundamental biology across species.