Co-regulation of microRNAs and transcription factors in cardiomyocyte specific differentiation of murine embryonic stem cells: An aspect from transcriptome analysis.

The differentiation process of embryonic stem cells is a comprehensive process regulated by a variety of factors in response to stimulus. Studies of this process can be focused on cell biology as well as on molecular biology level. In this paper we identified the co-regulation of molecular regulators and their interactions during cardiomyocyte specific differentiation of mouse embryonic stem cells based on parallel genome wide transcriptome analyses of mRNA and microRNA. Differentially expressed mRNAs and microRNAs were identified according to their expression profiles. Subsequently, a primary network was generated by using our genome wide profiling data, predicted sequence target information of transcription factors and microRNAs from various sources, validated microRNA target information, as well as tissue specific transcription factor binding information. Considering only validated microRNA target information and tissue specific transcription factor binding information secondary regulatory networks were extracted from the primary network to identify basic regulatory elements. Eight types of 3-node patterns were identified in this network. Novel regulatory modules, like Meis1 - Gata6 and miR-21/24 - Zic3, were discovered with high plausibility by this procedure without complicated and time-consuming experimental processes.