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...
Main Authors: | , , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2015-11-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715011419 |
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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 |
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