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

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...

Full description

Bibliographic Details
Main Authors: Lothar C. Dieterich, Sarah Klein, Anthony Mathelier, Adriana Sliwa-Primorac, Qiaoli Ma, Young-Kwon Hong, Jay W. Shin, Michito Hamada, Marina Lizio, Masayoshi Itoh, Hideya Kawaji, Timo Lassmann, Carsten O. Daub, Erik Arner, Piero Carninci, Yoshihide Hayashizaki, Alistair R.R. Forrest, Wyeth W. Wasserman, Michael Detmar
Format: Article
Language:English
Published: Elsevier 2015-11-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124715011419
_version_ 1818059805659496448
author Lothar C. Dieterich
Sarah Klein
Anthony Mathelier
Adriana Sliwa-Primorac
Qiaoli Ma
Young-Kwon Hong
Jay W. Shin
Michito Hamada
Marina Lizio
Masayoshi Itoh
Hideya Kawaji
Timo Lassmann
Carsten O. Daub
Erik Arner
Piero Carninci
Yoshihide Hayashizaki
Alistair R.R. Forrest
Wyeth W. Wasserman
Michael Detmar
author_facet Lothar C. Dieterich
Sarah Klein
Anthony Mathelier
Adriana Sliwa-Primorac
Qiaoli Ma
Young-Kwon Hong
Jay W. Shin
Michito Hamada
Marina Lizio
Masayoshi Itoh
Hideya Kawaji
Timo Lassmann
Carsten O. Daub
Erik Arner
Piero Carninci
Yoshihide Hayashizaki
Alistair R.R. Forrest
Wyeth W. Wasserman
Michael Detmar
author_sort Lothar C. Dieterich
collection DOAJ
description 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.
first_indexed 2024-12-10T13:22:22Z
format Article
id doaj.art-d61ccb55c64848fa87fa8dddc7cdee82
institution Directory Open Access Journal
issn 2211-1247
language English
last_indexed 2024-12-10T13:22:22Z
publishDate 2015-11-01
publisher Elsevier
record_format Article
series Cell Reports
spelling doaj.art-d61ccb55c64848fa87fa8dddc7cdee822022-12-22T01:47:17ZengElsevierCell Reports2211-12472015-11-011371493150410.1016/j.celrep.2015.10.002DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic EndotheliumLothar C. Dieterich0Sarah Klein1Anthony Mathelier2Adriana Sliwa-Primorac3Qiaoli Ma4Young-Kwon Hong5Jay W. Shin6Michito Hamada7Marina Lizio8Masayoshi Itoh9Hideya Kawaji10Timo Lassmann11Carsten O. Daub12Erik Arner13Piero Carninci14Yoshihide Hayashizaki15Alistair R.R. Forrest16Wyeth W. Wasserman17Michael Detmar18Institute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, SwitzerlandInstitute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, SwitzerlandCentre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4, CanadaInstitute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, SwitzerlandInstitute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, SwitzerlandDivision of Plastic and Reconstructive Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USADivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanDepartment of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, JapanDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanRIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, JapanDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, JapanCentre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4, CanadaInstitute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, SwitzerlandVEGF-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.http://www.sciencedirect.com/science/article/pii/S2211124715011419
spellingShingle Lothar C. Dieterich
Sarah Klein
Anthony Mathelier
Adriana Sliwa-Primorac
Qiaoli Ma
Young-Kwon Hong
Jay W. Shin
Michito Hamada
Marina Lizio
Masayoshi Itoh
Hideya Kawaji
Timo Lassmann
Carsten O. Daub
Erik Arner
Piero Carninci
Yoshihide Hayashizaki
Alistair R.R. Forrest
Wyeth W. Wasserman
Michael Detmar
DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium
Cell Reports
title DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium
title_full DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium
title_fullStr DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium
title_full_unstemmed DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium
title_short DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium
title_sort deepcage transcriptomics reveal an important role of the transcription factor mafb in the lymphatic endothelium
url http://www.sciencedirect.com/science/article/pii/S2211124715011419
work_keys_str_mv AT lotharcdieterich deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT sarahklein deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT anthonymathelier deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT adrianasliwaprimorac deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT qiaolima deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT youngkwonhong deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT jaywshin deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT michitohamada deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT marinalizio deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT masayoshiitoh deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT hideyakawaji deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT timolassmann deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT carstenodaub deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT erikarner deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT pierocarninci deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT yoshihidehayashizaki deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT alistairrrforrest deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT wyethwwasserman deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium
AT michaeldetmar deepcagetranscriptomicsrevealanimportantroleofthetranscriptionfactormafbinthelymphaticendothelium