Genetic Targeting of Organ-Specific Blood Vessels | |
Pu, Wenjuan1,2; He, Lingjuan1,2; Tian, Xueying1,2; Li, Yan1,2; Zhang, Hui1,3,4; Liu, Qiaozhen1,2; Huang, Xiuzhen1,2; Zhou, Bin1,2,3,4,8![]() | |
刊名 | CIRCULATION RESEARCH
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2018 | |
卷号 | 123期号:1页码:86-99 |
关键词 | Diphtheria-toxin Receptor Site-specific Recombinase Endothelial-cells Brain-barrier Angiocrine Signals Cre-loxp In-vivo Lineage Liver Mice |
ISSN号 | 0009-7330 |
DOI | 10.1161/CIRCRESAHA.118.312981 |
文献子类 | Article |
英文摘要 | Rationale: Organs of the body require vascular networks to supply oxygen and nutrients and maintain physiological function. The blood vessels of different organs are structurally and functionally heterogeneous in nature. To more precisely dissect their distinct in vivo function in individual organs, without potential interference from off-site targets, it is necessary to genetically target them in an organ-specific manner. Objective: The objective of this study was to generate a genetic system that targets vascular endothelial cells in an organ- or tissue-specific manner and to exemplify the potential application of intersectional genetics for precise, target-specific gene manipulation in vivo. Methods and Results: We took advantage of 2 orthogonal recombination systems, Dre-rox and Cre-loxP, to create a genetic targeting system based on intersectional genetics. Using this approach, Cre activity was only detectable in cells that had expressed both Dre and Cre. Applying this new system, we generated a coronary endothelial cell-specific Cre (CoEC-Cre) and a brain endothelial cell-specific Cre (BEC-Cre). Through lineage tracing, gene knockout and overexpression experiments, we demonstrated that CoEC-Cre and BEC-Cre efficiently and specifically target blood vessels in the heart and brain, respectively. By deletion of vascular endothelial growth factor receptor 2 using BEC-Cre, we showed that vascular endothelial growth factor signaling regulates angiogenesis in the central nervous system and also controls the integrity of the blood-brain barrier. Conclusions: We provide 2 examples to illustrate the use of intersectional genetics for more precise gene targeting in vivo, namely manipulation of genes in blood vessels of the heart and brain. More broadly, this system provides a valuable strategy for tissue-specific gene manipulation that can be widely applied to other fields of biomedical research. |
电子版国际标准刊号 | 1524-4571 |
WOS研究方向 | Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease |
语种 | 英语 |
WOS记录号 | WOS:000435962900014 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3410] ![]() |
专题 | 生化所2018年发文 上海生化细胞研究所_上海生科院生化细胞研究所 |
通讯作者 | Zhou, Bin |
作者单位 | 1.Univ Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol, Beijing, Peoples R China; 2.Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutrit Sci, Beijing, Peoples R China; 3.Shanghai Tech Univ, Shanghai Inst Biol Sci, Beijing, Peoples R China; 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 5.AstraZeneca, Biosci Heart Failure Cardiovasc & Metab Dis, IMED Biotech Unit, Gothenburg, Sweden; 6.Inst Biotechnol, Natl Ctr Prot Sci Beijing, Beijing Proteome Res Ctr, State Key Lab Prote,Beijing Inst Life,Lab Prote, Beijing, Peoples R China; 7.Univ Oxford, British Heart Fdn Ctr Regenerat Med, Dept Physiol Anat & Genet, Oxford, England; 8.Jinan Univ, Key Lab Regenerat Med, Minist Educ, Inst Aging & Regenerat Med, Guangzhou, Guangdong, Peoples R China |
推荐引用方式 GB/T 7714 | Pu, Wenjuan,He, Lingjuan,Tian, Xueying,et al. Genetic Targeting of Organ-Specific Blood Vessels[J]. CIRCULATION RESEARCH,2018,123(1):86-99. |
APA | Pu, Wenjuan.,He, Lingjuan.,Tian, Xueying.,Li, Yan.,Zhang, Hui.,...&Smart, Nicola.(2018).Genetic Targeting of Organ-Specific Blood Vessels.CIRCULATION RESEARCH,123(1),86-99. |
MLA | Pu, Wenjuan,et al."Genetic Targeting of Organ-Specific Blood Vessels".CIRCULATION RESEARCH 123.1(2018):86-99. |
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