DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium

作者：Dieterich Lothar C; Klein Sarah; Mathelier Anthony; Sliwa Primorac Adriana; Ma Qiaoli; Hong Young Kwon; Shin Jay W; Hamada Michito; Lizio Marina; Itoh Masayoshi; Kawaji Hideya; Lassmann Timo; Daub Carsten O; Arner Erik; Carninci Piero; Hayashizaki Yoshihide; Forrest Alistair R R; Wasserman Wyeth W; Detmar Michael^*

来源：Cell Reports, 2015, 13(7): 1493-1504.

DOI：10.1016/j.celrep.2015.10.002

VEGF-C/VEGFR-3 signaling plays a central role in lymphatic development, regulating the budding of lymphatic progenitor cells from embryonic veins and maintaining the expression of PROX1 during later developmental stages. However, how VEGFR-3 activation translates into target gene expression is still not completely understood. We used cap analysis of gene expression (CAGE) RNA sequencing to characterize the transcriptional changes invoked by VEGF-C in LECs and to identify the transcription factors (TFs) involved. We found that MAFB, a TF involved in differentiation of various cell types, is rapidly induced and activated by VEGF-C. MAFB induced expression of PROX1 as well as other TFs and markers of differentiated LECs, indicating a role in the maintenance of the mature LEC phenotype. Correspondingly, E14.5 Mafb(-/-) embryos showed impaired lymphatic patterning in the skin. This suggests that MAFB is an important TF involved in lymphangiogenesis.

• 出版日期2015-11-17