Defining the Mechanism of Transcription Factor-Induced Epigenetic Reprogramming.

Abstract SCI-41

The great excitement surrounding induced pluripotent stem (iPS) cells is tempered by the fact that little is known about how they are generated and why this process is so inefficient. We have set out to ask how the four transcription factors Oct4, Sox2, cMyc and Klf4 can induce pluripotency. By analyzing the role of the reprogramming factors Oct4, Sox2, Klf4 and cMyc during the initial step of reprogramming and comparing their binding and global expression in fully and partially reprogrammed cells, we previously uncovered that cMyc has a central role in the repression of the somatic cell expression program. With respect to the upregulation of the embryonic cell transcription, the four factors cooperate to activate the metabolic program, followed by binding of Oct4, Klf4 and Sox2 to genes encoding pluripotency regulators leading to the self-sustained, pluripotent state. Thus, we suggested that the factors have separable and temporal contributions to the reprogramming process. We are particularly interested in further deciphering the mechanism of reprogramming, understanding barriers of the reprogramming process, and comparing the embryonic stem cell state with the iPS cell state.