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Cell Rep. 2015 Nov 17;13(7):1493-1504. doi: 10.1016/j.celrep.2015.10.002. Epub 2015 Nov 5.

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

Author information

1
Institute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, Switzerland.
2
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
3
Division of Plastic and Reconstructive Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
4
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, Japan.
5
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
6
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, Japan; Telethon Kids Institute, The University of Western Australia, Subiaco, WA 6008, Australia.
7
RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, Japan.
8
Institute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, Switzerland. Electronic address: michael.detmar@pharma.ethz.ch.

Abstract

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.

PMID:
26549461
DOI:
10.1016/j.celrep.2015.10.002
[Indexed for MEDLINE]
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