Comparative analysis of mouse strains for in vivo induction of reprogramming factors

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.

Keywords: CP: Stem cell research; OSKM; aging; chimeric; in vivo; induction; rejuvenation; reprogramming; safety; strain; survival.