| 1 | Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition显示文摘The response of endothelial cells to signaling stimulation is critical for vascular morphogenesis,homeostasis and function.Vascular endothelial growth factor-a(VEGFA)has been commonly recognized as a pro-angiogenic factor in vertebrate developmental,physiological and pathological conditions for decades.Here we report a novel finding that genetic ablation of CDP-diacylglycerol synthetase-2(CDS2),a metabolic enzyme that controls phosphoinositide recycling,switches the output of VEGFA signaling from promoting angiogenesis to unexpectedly inducing vessel regression.Live imaging analysis uncovered the presence of reverse migration of the angiogenic endothelium in cds2 mutant zebrafish upon VEGFA stimulation,and endothelium regression also occurred in postnatal retina and implanted tumor models in mice.In tumor models,CDS2 deficiency enhanced the level of tumorsecreted VEGFA,which in-turn trapped tumors into a VEGFA-induced vessel regression situation,leading to suppression of tumor growth.Mechanistically,VEGFA stimulation reduced phosphatidylinositol(4,5)-bisphosphate(PIP2)availability in the absence of CDS2-controlled-phosphoinositide metabolism,subsequently causing phosphatidylinositol(3,4,5)-triphosphate(PIP3)deficiency and F0X01 activation to trigger regression of CDS2-null endothelium.Thus,our data indicate that the effect of VEGFA on vasculature is context-dependent and can be converted from angiogenesis to vascular regression. | Wencao Zhao Le Cao Hanru Ying Wenjuan Zhang Dantong Li Xiaolong Ziiu Wenzhi Xue Shuang Wu Mengye Cao Cong Fu Haonan Qi Yimei Hao Yun-Chi Tang Jun Qin Tao PZhong Xiaoxi Lin Luyang Yu Xuri Li Lin Li Dianqing Wu Weijun Pan | 2019 | Cell Research2019，29，11： | 9 |
| 2 | Differentiation and Pro-Angiogenic Potential of Infantile Hemangioma Stem Cells显示文摘Objectives Infantile hemangioma(IH)is defined as a benign vascular tumor composed of immature vascular endothelial cells,with the unique characteristics of rich vascularization and self-regression into fibro-fatty tissue.CD133-positive hemangioma stem cells(HemSCs),present in the proliferating IH tissue,can be used to establish the IH animal model,which has highlighted the pathogenesis of IH in recent years.This study focused on the biological characteristics and differentiation capacity of HemSCs and aimed to provide a theoretical possibility for its application in tissue engineering.Methods To further confirm our hypothesis,we used fluorescence-activated cell sorting(FACS),in vitro multipotent induced differentiation,angiogenesis assay,and antibody array to identify the surface markers,multipotent differential potential,angiogenesis potential,and secreted factors of HemSCs,respectively,utilizing human adipose stem cells(hADSCs)as the control.Results We successfully isolated and cultured HemSCs.FACS indicated that,on average,more than 80%of HemSCs matched the criteria of mesenchymal stem cell(MSC)surface markers.Our results confirmed that HemSCs could differentiate into adipocytes,osteocytes,and chondrocytes.Additionally,compared with fibroblasts or hADSCs,HemSCs could promote angiogenesis through para-secretion.Conclusions HemSCs may originate from normal MSCs,and owing to their powerful proliferative and angiogenic abilities,they could be considered an IH pathogenic factor.These characteristics demonstratet heir potential as a candidate seed cell in tissue engineering. | Hanru YING Qianyi CHEN Xuanfeng CHEN Zhang YU MD Shih-Jen CHANG Lei CHANG Gang MA Yajing QIU Hui CHEN Xiaoxi LIN | 2020 | Chinese Journal Of Plastic and Reconstructive Surgery2020，2，1： | 2 |
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