Abstract
Trans-differentiation of cells through direct reprogramming offers significant potential for regenerative medicine and drug screen, but currently it requires exhaustive trials and errors before the desired target cells can be created. Based on the comprehensive transcriptome analyses by the FANTOM consortium, in particular the recently published transcriptional regulatory network analysis, we have developed a systematic method for direct reprogramming and succeeded in creating monocyte-like cells with several monocyte-specific functions. Further analysis of the created cells reveals that the transcriptional regulatory networks and the epigenomes of the original terminally differentiated cells act as strong barriers that prevent easy reprogramming by extra stimuli. These biological insights should be carefully considered for efficient and complete direct reprogramming.