PRDM16 regulates arterial development and vascular integrity
Proper vascular formation is regulated by multiple signaling pathways. The vascular endothelial growth factor (VEGF) signaling promotes endothelial proliferation. Notch and its downstream targets act to lead endothelial cells toward an arterial fate through regulation of arterial gene expression. Ho...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1165379/full |
| _version_ | 1797814252930596864 |
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| author | Michael Thompson Michael Thompson Masahide Sakabe Masahide Sakabe Mark Verba Mark Verba Jiukuan Hao Stryder M. Meadows Stryder M. Meadows Q. Richard Lu Q. Richard Lu Mei Xin Mei Xin |
| author_facet | Michael Thompson Michael Thompson Masahide Sakabe Masahide Sakabe Mark Verba Mark Verba Jiukuan Hao Stryder M. Meadows Stryder M. Meadows Q. Richard Lu Q. Richard Lu Mei Xin Mei Xin |
| author_sort | Michael Thompson |
| collection | DOAJ |
| description | Proper vascular formation is regulated by multiple signaling pathways. The vascular endothelial growth factor (VEGF) signaling promotes endothelial proliferation. Notch and its downstream targets act to lead endothelial cells toward an arterial fate through regulation of arterial gene expression. However, the mechanisms of how endothelial cells (ECs) in the artery maintain their arterial characteristics remain unclear. Here, we show that PRDM16 (positive regulatory domain-containing protein 16), a zinc finger transcription factor, is expressed in arterial ECs, but not venous ECs in developing embryos and neonatal retinas. Endothelial-specific deletion of Prdm16 induced ectopic venous marker expression in the arterial ECs and reduced vascular smooth muscle cell (vSMC) recruitment around arteries. Whole-genome transcriptome analysis using isolated brain ECs show that the expression of Angpt2 (encoding ANGIOPOIETIN2, which inhibits vSMC recruitment) is upregulated in the Prdm16 knockout ECs. Conversely, forced expression of PRDM16 in venous ECs is sufficient to induce arterial gene expression and repress the ANGPT2 level. Together, these results reveal an arterial cell-autonomous function for PRDM16 in suppressing venous characteristics in arterial ECs. |
| first_indexed | 2024-03-13T08:04:53Z |
| format | Article |
| id | doaj.art-0fc61f87e65e4accb9d436070d566b1d |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-03-13T08:04:53Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-0fc61f87e65e4accb9d436070d566b1d2023-06-01T05:23:50ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-06-011410.3389/fphys.2023.11653791165379PRDM16 regulates arterial development and vascular integrityMichael Thompson0Michael Thompson1Masahide Sakabe2Masahide Sakabe3Mark Verba4Mark Verba5Jiukuan Hao6Stryder M. Meadows7Stryder M. Meadows8Q. Richard Lu9Q. Richard Lu10Mei Xin11Mei Xin12Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesDivision of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesDivision of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United StatesCell and Molecular Biology Department, Tulane University, New Orleans, LA, United StatesTulane Brain Institute, Tulane University, New Orleans, LA, United StatesDivision of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesDivision of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesProper vascular formation is regulated by multiple signaling pathways. The vascular endothelial growth factor (VEGF) signaling promotes endothelial proliferation. Notch and its downstream targets act to lead endothelial cells toward an arterial fate through regulation of arterial gene expression. However, the mechanisms of how endothelial cells (ECs) in the artery maintain their arterial characteristics remain unclear. Here, we show that PRDM16 (positive regulatory domain-containing protein 16), a zinc finger transcription factor, is expressed in arterial ECs, but not venous ECs in developing embryos and neonatal retinas. Endothelial-specific deletion of Prdm16 induced ectopic venous marker expression in the arterial ECs and reduced vascular smooth muscle cell (vSMC) recruitment around arteries. Whole-genome transcriptome analysis using isolated brain ECs show that the expression of Angpt2 (encoding ANGIOPOIETIN2, which inhibits vSMC recruitment) is upregulated in the Prdm16 knockout ECs. Conversely, forced expression of PRDM16 in venous ECs is sufficient to induce arterial gene expression and repress the ANGPT2 level. Together, these results reveal an arterial cell-autonomous function for PRDM16 in suppressing venous characteristics in arterial ECs.https://www.frontiersin.org/articles/10.3389/fphys.2023.1165379/fullPRDM16vascular developmentangiogenesisangiopoietinartery |
| spellingShingle | Michael Thompson Michael Thompson Masahide Sakabe Masahide Sakabe Mark Verba Mark Verba Jiukuan Hao Stryder M. Meadows Stryder M. Meadows Q. Richard Lu Q. Richard Lu Mei Xin Mei Xin PRDM16 regulates arterial development and vascular integrity Frontiers in Physiology PRDM16 vascular development angiogenesis angiopoietin artery |
| title | PRDM16 regulates arterial development and vascular integrity |
| title_full | PRDM16 regulates arterial development and vascular integrity |
| title_fullStr | PRDM16 regulates arterial development and vascular integrity |
| title_full_unstemmed | PRDM16 regulates arterial development and vascular integrity |
| title_short | PRDM16 regulates arterial development and vascular integrity |
| title_sort | prdm16 regulates arterial development and vascular integrity |
| topic | PRDM16 vascular development angiogenesis angiopoietin artery |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1165379/full |
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