title: Genetic targeting of sprouting angiogenesis using Apln-CreER.
abstract: Under pathophysiological conditions in adults, endothelial cells (ECs) sprout from pre-existing blood vessels to form new ones by a process termed angiogenesis. During embryonic development, Apelin (APLN) is robustly expressed in vascular ECs. In adult mice, however, APLN expression in the vasculature is significantly reduced. Here we show that APLN expression is reactivated in adult ECs after ischaemia insults. In models of both injury ischaemia and tumor angiogenesis, we find that Apln-CreER genetically labels sprouting but not quiescent vasculature. By leveraging this specific activity, we demonstrate that abolishment of the VEGF-VEGFR2 signalling pathway as well as ablation of sprouting ECs diminished tumour vascularization and growth without compromising vascular homeostasis in other organs. Collectively, we show that Apln-CreER distinguishes sprouting vessels from stabilized vessels in multiple pathological settings. The Apln-CreER line described here will greatly aid future mechanistic studies in both vascular developmental biology and adult vascular diseases.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Qiaozhen
authors.initials: Q
authors.lastname: Liu
authors.affiliation: 1] Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China [2] Life and Brain Center, Institute of Physiology I, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Hu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: He
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Huang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Tian
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Liang
authors.initials: L
authors.lastname: He
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Pu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.
authors.forename: Shengzhong
authors.initials: S
authors.lastname: Duan
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chaobo
authors.initials: C
authors.lastname: Hu
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
authors.affiliation: Fifth Department of Hepatic Surgery, Eastern Hepatobilliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre, London SE5 9NU, UK.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Kristy
authors.initials: K
authors.lastname: Red-Horse
authors.affiliation: Department of Molecular Physiology and Biophysics, Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Wythe
authors.affiliation: 1] Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China [2] CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
mesh_terms: D054392:Adipokines; D000818:Animals; D000073861:Apelin; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006614:Hindlimb; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007511:Ischemia; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2