Mechanisms of somatic cell reprogramming

Abstract

Generation of induced pluripotent stem cells (iPSCs) from somatic cell types has revolutionized the field of stem cell biology and opened the way for production of disease- and patient-specific stem cells which have tremendous potential for regenerative medicine. Despite the rapid progress and improvement in iPSC-derivation techniques, transcription factor-based reprogramming remains an inefficient and poorly understood process. Successful reprogramming requires the completion of a number of rate-limiting steps that include avoiding senescence, mesenchymal-epithelial transition, and activation of endogenous pluripotency genes. It has also become clear that the global epigenetic landscape of the somatic cell types is completely overhauled during acquisition of pluripotency. The epigenetic state is largely determined by the deposition of chromatin marks which include histone tail modifications and DNA methylation. These marks are not only indicative of a given cell state; they are also functionally important during reprogramming. In this chapter I will review our current understanding of the mechanism of reprogramming and the role chromatin marks and the associated chromatin-modifier proteins play in this process.