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

L.C. Dieterich, S. Klein, A. Mathelier, A. Sliwa-Primorac, Q. Ma, Y.K. Hong, J.W. Shin, M. Hamada, M. Lizio, M. Itoh, H. Kawaji, Timo Lassmann, C.O. Daub, E. Arner, P. Carninci, Y. Hayashizaki, A.R.R. Forrest, W.W. Wasserman, M. Detmar

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

© 2015 The Authors. 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.
Original languageEnglish
Pages (from-to)1493-1504
JournalCell Reports
Volume13
Issue number7
DOIs
Publication statusPublished - 2015

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