Chromatin structure, pluripotency and differentiation

Abstract

The state of cell differentiation in adult tissues was once thought to be permanent and irreversible. Since Dolly's cloning and, more recently, the generation of induced pluripotent stem cells (iPSCs) from differentiated cells, the traditional paradigm of cell identity has been reexamined. Much effort has been directed toward understanding how cellular identity is achieved and maintained, and studies are ongoing to investigate how cellular identity can be changed. Cell-specific transcription patterns can be altered by modulating the expression of a few transcription factors, which are known as master regulators of cell fate. Epigenetics also plays a major role in cell type specification because the differentiation process is accompanied by major chromatin remodeling. Moreover, whole-genome analyses reveal that nuclear architecture, as defined by the establishment of chromatin domains, regulates gene interactions in a cell-type-specific manner. In this paper, we review the current knowledge of chromatin states that are relevant to both pluripotency and gene expression during differentiation. Information about the epigenetic regulation of gene expression in iPSCs or naïve embryonic stem cells, compared with their differentiated derivatives, will be important as a practical consideration in the long-term maintenance of pluripotent cell cultures for therapeutic purposes.