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

Abstract

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.