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Updated: Sep 18, 2025
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Published on: November 29, 2012
Comparative analysis of mouse strains for in vivo induction of reprogramming factors
Sara Picó1, Alba Vílchez-Acosta1, João Agostinho de Sousa2
1Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Abstract:
In vivo reprogramming through the forced expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) has demonstrated great potential for reversing age-associated phenotypes. However, continuous in vivo OSKM expression has raised safety concerns due to loss of cell identity, decrease in body weight, and premature death. Although cyclic short-term or targeted expression of the reprogramming factors can mitigate some of these detrimental effects, systemic rejuvenation of wild-type mice has remained elusive. To improve the fundamental understanding of in vivo reprogramming, we conduct a comparative analysis of various reprogrammable mouse strains across multiple tissues and organs. In addition, we develop reprogrammable mouse strains by avoiding OSKM expression in specific organs or implementing expression approaches within specific cells, thereby offering safer strategies to induce in vivo reprogramming. We hope that these tools will become valuable resources for future research in this field of research with potential implications to human health.
Insights
Forced expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) can reverse aging, but continuous use causes harm. New mouse models offer safer strategies for in vivo reprogramming and potential human health benefits.
Area of Science:
- Cellular reprogramming
- Aging research
- Genetics
Background:
- In vivo reprogramming using Oct4, Sox2, Klf4, and c-Myc (OSKM) shows promise for reversing age-related changes.
- However, continuous OSKM expression leads to safety issues like cell identity loss, weight reduction, and early mortality.
Purpose of the Study:
- To compare different reprogrammable mouse strains for in vivo reprogramming across various tissues.
- To develop novel reprogrammable mouse models with safer strategies for targeted or cell-specific OSKM expression.
Main Methods:
- Comparative analysis of existing reprogrammable mouse strains.
- Development of new mouse models with organ-specific or cell-specific OSKM expression control.
Main Results:
- Identified variations in in vivo reprogramming across different mouse strains and tissues.
- Successfully engineered mouse models with controlled OSKM expression, mitigating adverse effects.
Conclusions:
- Controlled, targeted in vivo reprogramming strategies are crucial for safety and efficacy.
- The developed mouse models serve as valuable tools for future research in rejuvenation and human health.
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