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Red2Flpe-SCON: a versatile, multicolor strategy for generating mosaic conditional knockout mice.
Szu-Hsien Sam Wu1,2, Somi Kim3, Heetak Lee4
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria.
Nature Communications
|June 11, 2024
Summary
A new Red2Flpe-SCON mouse model allows multicolor lineage tracing of mutant and wild-type cells. This system revealed that the Sox2 gene is crucial for stem cell proliferation and differentiation, not maintenance.
Area of Science:
- Developmental Biology
- Genetics
- Stem Cell Biology
Background:
- Image-based lineage tracing is vital for studying tissue dynamics and cell potential.
- Previous Red2Onco models facilitated oncogenic clone analysis.
- A need exists for systems that can track both mutant and wild-type cells simultaneously.
Purpose of the Study:
- To develop a novel mosaic knockout system for multicolor lineage tracing.
- To investigate the role of Sox2 in adult stem cell function using this new system.
Main Methods:
- Development of the Red2Flpe mouse line for clone-specific Flpe expression.
- Implementation of the FRT-based SCON (Short Conditional IntrON) method for tunable mosaic knockouts.
- Application of the Red2Flpe-SCON system for Sox2 mutant clonal analysis in mouse esophageal epithelium.
Main Results:
- The Red2Flpe-SCON system enables multicolor labeling of mutant and wild-type cells.
- Sox2 mutant clonal analysis in the esophageal epithelium was successfully performed.
- Sox2 was found to be less critical for stem cell maintenance but essential for proliferation and differentiation.
Conclusions:
- The Red2Flpe-SCON system is a powerful tool for mosaic analysis in vivo.
- Sox2 plays a critical role in regulating adult stem cell proliferation and differentiation.
- This study refines our understanding of stem cell gene function in tissue homeostasis.
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