Red2Flpe-SCON: a versatile, multicolor strategy for generating mosaic conditional knockout mice.
Szu-Hsien Sam WuSomi KimHeetak LeeJi-Hyun LeeSo-Yeon ParkRéka BakonyiIsaree TeriyapiromNatalia HallaySandra Pilat-CarottaHans-Christian TheusslJihoon KimJoo-Hyeon LeeBenjamin David SimonsJong Kyoung KimGabriele ColozzaBon-Kyoung KooPublished in: Nature communications (2024)
Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation.
Keyphrases
- wild type
- stem cells
- cell proliferation
- mouse model
- single cell
- genome wide
- transcription factor
- poor prognosis
- gene expression
- induced apoptosis
- type diabetes
- copy number
- young adults
- quantum dots
- skeletal muscle
- high fat diet induced
- oxidative stress
- signaling pathway
- flow cytometry
- insulin resistance
- genome wide identification