| Lymphocyte mainly includes B cell and T cell, which develops from common lymphoid progenitors(C LPs) that go through various continuous and characteristic stages. The maturation process of lymphocyte is related to several of blood diseases such as lymphocytic leukemia and lymphoma. Many transcription factors(TFs) and micro RNAs(miRNAs) have been found to be involved in lymphocyte development, but the co-regulation mechanism is still unknown. This research fully collected the available data, and tried to understand the development of lymphocytes from the perspective of co-regulation of TFs with miRNA.First, we obtained the candidate genes, miRN As and TFs at each stage of their maturation process by searching the available literature and related database, and then constructed the TF- miRNA-gene feed- forward loops(FFLs) for each stage using a variety of bioinformatics tools, and designed a permutation test model to test the FFLs. Statistical test for FFLs indicated their enrichment and significance. Further, the TF- miRNA co-regulatory networks for each stage were constructed by combining their FFLs.We compared and analyzed the FFLs and network for each stage of B and T cell maturation. Hub analysis revealed the key regulators in each stage, for example, MYC, STAT5 A, PAX5 and miR-17~92 in the transition of pro-B cells into pre-B cells, RUNX3 and NANOG in the determining of CD4/CD8 T cell lineage. We also identified a few common regulators and modules in two stages of B cell maturation(e.g. miR-146a/NFKB1/BC L11 A) and two stages of T cell maturation(e.g. miR-20/CCND2/ SORL1), as well as some shared regulators and modules in the early stages of both B and T cell development(e.g. STAT5A/miR-20a/ CCND2).Conclusion: The TF and miRNA co-regulatory network is a feasible method to identify key regulators and modules in biological processes and diseases. Our results will help to understand the mature process of B/T cell, as well as the related blood diseases. |
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