Background: The great variety of human cell types develops from a single fertilized egg, a process that is governed by regulatory networks controlling the required genetic programs.It is still a challenging task to explain how the regulatory networks of different cells can emerge from the information pool of one genome.Methods: We investigated the design principles of the tissue regulatory system by constructing the regulatory networks of eight human tissues, which subsume the regulatory interactions between transcription factors (TFs), microRNAs (miRNAs) and non-TF target genes.The network topology and network motifs were calculated for the discovery of gene network properties.Results: The results show that there are in-/out-hubs of high in-/out-degrees in the tissue networks.The strong hubs maintain the hub status in all the tissues where they are expressed, whereas the weak hubs are only in some tissues, in spite of their ubiquitous expression of the corresponding genes.The network motifs are mostly feed-forward loops.Some of them without miRNA are the common motifs shared by all tissues, whereas the others containing miRNAs are the tissue-specific ones owned by one or more tissues, indicating that the transcriptional regulation is more conserved across tissues than the post-transcriptional regulation.In particular, a common bow-tie framework underlying the motif instances was found that shows diverse pattems in different tissues.Conclusions: Such bow-tie framework comprises the efficiency of gene regulatory system and its high variability in different tissues, and could be the model to further understand the structural evolution of regulatory system during cell differentiation.Our study elucidates the architecture of regulatory systems in human tissues and benefits the understanding of regulatory mechanisms underlying the processes of cell differentiation .