Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells
Understanding epigenetic mechanisms regulating embryonic stem cell (ESC) differentiation to endothelial cells may lead to increased efficiency of generation of vessel wall endothelial cells needed for vascular engineering. Here we demonstrated that the histone demethylases KDM4A and KDM4C played an...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-07-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115001599 |
| _version_ | 1828765387794153472 |
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| author | Liangtang Wu Kishore K. Wary Sergei Revskoy Xiaopei Gao Kitman Tsang Yulia A. Komarova Jalees Rehman Asrar B. Malik |
| author_facet | Liangtang Wu Kishore K. Wary Sergei Revskoy Xiaopei Gao Kitman Tsang Yulia A. Komarova Jalees Rehman Asrar B. Malik |
| author_sort | Liangtang Wu |
| collection | DOAJ |
| description | Understanding epigenetic mechanisms regulating embryonic stem cell (ESC) differentiation to endothelial cells may lead to increased efficiency of generation of vessel wall endothelial cells needed for vascular engineering. Here we demonstrated that the histone demethylases KDM4A and KDM4C played an indispensable but independent role in mediating the expression of fetal liver kinase (Flk)1 and VE-cadherin, respectively, and thereby the transition of mouse ESCs (mESCs) to endothelial cells. KDM4A was shown to bind to histones associated with the Flk1 promoter and KDM4C to bind to histones associated with the VE-cadherin promoter. KDM4A and KDM4C were also both required for capillary tube formation and vasculogenesis in mice. We observed in zebrafish that KDM4A depletion induced more severe vasculogenesis defects than KDM4C depletion, reflecting the early involvement of KDM4A in specifying endothelial cell fate. These findings together demonstrate the essential role of KDM4A and KDM4C in orchestrating mESC differentiation to endothelial cells through the activation of Flk1 and VE-cadherin promoters, respectively. |
| first_indexed | 2024-12-11T06:46:58Z |
| format | Article |
| id | doaj.art-2ab33cc85d904deea7325ba1242d270b |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-11T06:46:58Z |
| publishDate | 2015-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-2ab33cc85d904deea7325ba1242d270b2022-12-22T01:17:02ZengElsevierStem Cell Reports2213-67112015-07-0151102110.1016/j.stemcr.2015.05.016Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial CellsLiangtang Wu0Kishore K. Wary1Sergei Revskoy2Xiaopei Gao3Kitman Tsang4Yulia A. Komarova5Jalees Rehman6Asrar B. Malik7Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USAUnderstanding epigenetic mechanisms regulating embryonic stem cell (ESC) differentiation to endothelial cells may lead to increased efficiency of generation of vessel wall endothelial cells needed for vascular engineering. Here we demonstrated that the histone demethylases KDM4A and KDM4C played an indispensable but independent role in mediating the expression of fetal liver kinase (Flk)1 and VE-cadherin, respectively, and thereby the transition of mouse ESCs (mESCs) to endothelial cells. KDM4A was shown to bind to histones associated with the Flk1 promoter and KDM4C to bind to histones associated with the VE-cadherin promoter. KDM4A and KDM4C were also both required for capillary tube formation and vasculogenesis in mice. We observed in zebrafish that KDM4A depletion induced more severe vasculogenesis defects than KDM4C depletion, reflecting the early involvement of KDM4A in specifying endothelial cell fate. These findings together demonstrate the essential role of KDM4A and KDM4C in orchestrating mESC differentiation to endothelial cells through the activation of Flk1 and VE-cadherin promoters, respectively.http://www.sciencedirect.com/science/article/pii/S2213671115001599 |
| spellingShingle | Liangtang Wu Kishore K. Wary Sergei Revskoy Xiaopei Gao Kitman Tsang Yulia A. Komarova Jalees Rehman Asrar B. Malik Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells Stem Cell Reports |
| title | Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells |
| title_full | Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells |
| title_fullStr | Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells |
| title_full_unstemmed | Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells |
| title_short | Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells |
| title_sort | histone demethylases kdm4a and kdm4c regulate differentiation of embryonic stem cells to endothelial cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213671115001599 |
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