Epigenetics of cellular reprogramming

Abstract

Cells are constantly changing their state of equilibrium in response to internal and external stimuli. These changes in cell identity are driven by highly coordinated modulation of gene expression. This coordinated regulation is achieved in large part due to changes in the structure and composition of the chromatin, driven by epigenetic modulators. Recent discoveries in cellular and genomic reprogramming have highlighted the importance of chromatin modifications to reach and uphold the fidelity of target cell states. In this review, we focus on the latest work addressing the mechanisms surrounding the epigenetic regulation of various types of reprogramming, including somatic cell nuclear transfer (SCNT), cell fusion and transcription factor-induced and microRNA-induced pluripotency. The studies covered herein showcase the interplay between these epigenetic pathways, and highlight the importance of furthering our understanding of these connections to form a clearer picture of the mechanisms underlying stable cell fate transitions.

Fig. 1

Key epigenetic changes during the transition between differentiated and pluripotent cells.

Fig. 2

Pathways influencing the epigenetics of reprogramming. Green text -known enhancers of reprogramming. Red text - known inhibitors of reprogramming. Black text - unknown, unclear, or many different effects on reprogramming. Solid lines represent known connections and dashed lines represent speculative connections between factors.

Fig. 3

Unanswered questions in the field of transdifferentiation. Transitioning from one cell type to another could involve going through a pluripotent state, the nearest common progenitor state, or one or more unknown states.