Transcription factor and miRNA co-regulatory network reveals shared and specific regulators in the development of B...

The maturation process of lymphocyte was related to many blood diseases, such as lymphoma and lymphoid leukemia. Many TFs and miRNAs were separately studied in the development of B and T cells. In this study, we aim to discover the TF and miRNA co-regulation and identify key regulators in the B and T cells maturation. We obtained the candidate genes, miRNAs and TFs for each stage of their maturation, then constructed the TF-miRNA-gene feed-forward loops (FFLs) for each stage by our previous methods. Statistical test for FFLs indicated their enrichment and significance. TF-miRNA co-regulatory networks for each stage were constructed by combining their FFLs. Hub analysis revealed the key regulators in each stage, for example, MYC, STAT5A, PAX5 and miR-17 ~ 92 in the transition of pro-B cells into pre-B cells. We also identified a few common regulators and modules in two stages of B cell maturation (e.g. miR-146a/NFKB1/BCL11A) and two stages of T cell maturation (e.g. miR-20/CCND2/SORL1), as well as some shared regulators in the early stages of both B and T cell development. Our network will help to increase understanding of mature process of B and T cell, as well as the related blood diseases.