Vilchez Acosta, A. | Search bioRxiv

bioRxiv2024

In vivo reprogramming of Caenorhabditis elegans leads to heterogeneous effects on lifespan

In the last decade, cellular reprogramming of fully differentiated cells to pluripotent stem cells has become of great interest. Importantly, cellular reprogramming by expression of Oct4, Sox2, Klf4, and cMyc (OSKM) can ameliorate age-associated phenotypes in multiple tissues and extend lifespan in progeroid and aged wild-type mice. Surprisingly, the effects of in vivo reprogramming have not been deeply investigated in any other model organisms. Here, for the first time, we induce in vivo reprogramming in C. elegans using a heat-inducible system at multiple developmental and adult stages. Similar to mice, expression of the reprogramming factors leads to premature death with different levels of toxicity at distinct developmental stages and aging. In vivo reprogramming in C. elegans might represent a valuable tool to improve our understanding of development and in vivo reprogramming.

cell biology↗

bioRxiv2024

Comparative analysis of mouse strains for in vivo reprogramming

In vivo reprogramming through the forced expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) has demonstrated great potential for reversing age-associated phenotypes, as the combination of these transcription factors actively promote cell regeneration and rejuvenation in various tissues and organs. However, continuous in vivo OSKM expression 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 in mice, systemic rejuvenation of wild type mice has remained elusive potentially due to these current technical limitations. To improve the fundamental understanding of in vivo reprogramming, we conducted a comparative analysis across multiple reprogrammable mouse strains, tissues, and expression methods, presenting a comprehensive atlas of formerly established strains. In addition, we developed novel reprogrammable mouse strains by avoiding OSKM expression in specific organs, in dividing cells, or implementing chimeric expression approaches within specific cells, thereby offering safer strategies to induce in vivo reprogramming and fully harness its potential. We hope that these new tools will become valuable resources for future research in this very exciting field of research with potential implications to human health.

molecular biology↗