Deciphering the roadmap of in vivo reprogramming towards pluripotency

Abstract

Differentiated cells can be converted to pluripotent stem cells (iPSCs) upon ectopic expression of transcription factors OCT4, SOX2, KLF4 and MYC (OSKM) in a process known as reprogramming. Great efforts have been made to dissect intermediate states of in vitro reprogramming and how they are affected by culture conditions, while the roadmap of in vivo reprogramming remains unexplored. Here, we use single cell RNA sequencing to capture cells undergoing reprogramming in the adult pancreas. We identify markers along the trajectory from acinar identity to pluripotency, which allow in situ visualization of the intermediate states of reprogramming. Importantly, different tissues expressing OSKM, such as pancreas, stomach and colon, share markers of intermediate reprogramming, suggesting a conserved in vivo reprogramming path. Our in vivo roadmap defines landmarks along in vivo reprogramming that could be useful for applications in tissue regeneration and cellular rejuvenation based on intermediate reprogramming states.