机构：[1]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China[2]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[3]Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, College of Life Sciences, Peking University, Beijing 100871, China[4]University of the Chinese Academy of Sciences, Beijing 100049, China[5]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China[6]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China首都医科大学宣武医院衰老与再生研究中心国家老年疾病临床医学研究中心[7]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China[8]Institute for Advanced Co-Creation Studies, Graduate School of Engineering Science, Osaka University, Osaka 560-8531, Japan[9]Graduate School of Engineering Science, Osaka University, Osaka 560-8531, Japan[10]Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA[11]Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China[12]Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China[13]Beijing Institute for Brain Disorders, Beijing 100069, China[14]Army Diagnosis and Treatment Center for Oral Disease, 306th Hospital of the PLA, Beijing 100101, China
FOXO3 is an evolutionarily conserved transcription factor that has been linked to longevity. Here we wanted to find out whether human vascular cells could be functionally enhanced by engineering them to express an activated form of FOXO3. This was accomplished via genome editing at two nucleotides in human embryonic stem cells, followed by differentiation into a range of vascular cell types. FOXO3-activated vascular cells exhibited delayed aging and increased resistance to oxidative injury compared with wild-type cells. When tested in a therapeutic context, FOXO3-enhanced vascular cells promoted vascular regeneration in a mouse model of ischemic injury and were resistant to tumorigenic transformation both in vitro and in vivo. Mechanistically, constitutively active FOXO3 conferred cytoprotection by transcriptionally downregulating CSRP1. Taken together, our findings provide mechanistic insights into FOXO3-mediated vascular protection and indicate that FOXO3 activation may provide a means for generating more effective and safe biomaterials for cell replacement therapies.
基金：
National Key Research and Development Program of China [2015CB964800, 2018YFA0107203, 2017YFA0103304, 2017YFA0102802, 2014CB910503, 2018YFC2000100]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010100]; National Natural Science Foundation of China, China [81422017, 81625009, 81330008, 91749202, 91749123, 31671429, 81671377, 81771515, 31601109, 31601158, 81701388, 81601233, 81471414, 81870228, 81822018, 81801399, 31801010, 81801370, 81861168034]; Program of Beijing Municipal Science and Technology Commission [Z151100003915072]; Key Research Program of the Chinese Academy of Sciences [KJZDEWTZ-L05]; Beijing Municipal Commission of Health and Family Planning [PXM2018_026283_000002]; Advanced Innovation Center for Human Brain Protection [117212];
第一作者机构：[1]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China[2]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[4]University of the Chinese Academy of Sciences, Beijing 100049, China
共同第一作者：
通讯作者：
通讯机构：[1]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China[2]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[3]Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, College of Life Sciences, Peking University, Beijing 100871, China[4]University of the Chinese Academy of Sciences, Beijing 100049, China[6]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China[7]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China[11]Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China[12]Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China[13]Beijing Institute for Brain Disorders, Beijing 100069, China
推荐引用方式(GB/T 7714)：
Pengze Yan ,Qingqing Li ,Lixia Wang ,et al.FOXO3-Engineered Human ESC-Derived Vascular Cells Promote Vascular Protection and Regeneration[J].CELL STEM CELL.2019,24(3):447-+.doi:10.1016/j.stem.2018.12.002.
APA：
Pengze Yan,,Qingqing Li,,Lixia Wang,,Ping Lu,,Keiichiro Suzuki,...&Guang-Hui Liu.(2019).FOXO3-Engineered Human ESC-Derived Vascular Cells Promote Vascular Protection and Regeneration.CELL STEM CELL,24,(3)
MLA：
Pengze Yan,,et al."FOXO3-Engineered Human ESC-Derived Vascular Cells Promote Vascular Protection and Regeneration".CELL STEM CELL 24..3(2019):447-+
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