首页|Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological conditions.However,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive.Here,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MSCs),as a platform for discovering cell type-specific hypox-ia-induced response mechanisms.Through comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration.We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1α,impaired pro-angiogenic processes.Altogether,our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

HIF-1human ESCvascular cellregeneration

Jinghui Lei、Xiaoyu Jiang、Daoyuan Huang、Ying Jing、Shanshan Yang、Lingling Geng、Yupeng Yan、Fangshuo Zheng、Fang Cheng、Weiqi Zhang、Juan Carlos Izpisua Belmonte、Guang-Hui Liu、Si Wang、Jing Qu

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Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China

Aging Translational Medicine Center,International Center for Aging and Cancer,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China

State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China

University of Chinese Academy of Sciences,Beijing 100049,China

Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China

The Fifth People's Hospital of Chongqing,Chongqing 400062,China

National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Beijing 100101,China

CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China

China National Center for Bioinformation,Beijing 100101,China

Sino-Danish College,University of Chinese Academy of Sciences,Beijing 101408,China

Sino-Danish Center for Education and Research,Beijing 101408,China

Aging Biomarker Consortium,China

Altos Labs,San Diego,CA 92121,United States

Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China

Aging Biomarker C

State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China

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National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaStrategic Priority Research Program of the Chinese Academy of SciencesCAS Project for Young Scientists in Basic ResearchCAS Project for Young Scientists in Basic ResearchProgram of the Beijing Natural Science FoundationPilot Project for Public Welfare Development and Reform of Beijingaffiliated Medical Research InstitutesExcellent Young Talents Program of Capital Medical UniversityExcellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher TeamYouth Innovation Promotion Association of CASYoung Elite Scientists Sponsorship Program by CASTInformatization Plan of Chinese Academy of SciencesInformatization Plan of Chinese Academy of SciencesInformatization Plan of Chinese Academy of SciencesFellowship of China Postdoctoral Science FoundationTencent Foundation(2021-1045)

2020YFA08040002022YFA11037002020YFA01122002021YFF1201005the STI2030-Major Projects-2021ZD020240081921006821250119214930192168201919492099204930492049116321210018219286382122024820715888XDA16000000YSBR-076YSBR-012Z19001911000022T00000046106212300927BPHR202203105E1CAZW0401YESS20200012CAS-WX2021SF-0301CAS-WX2022SDC-XK14CAS-WX2021SF-01012022M712216

2024

10.1093/procel/pwad027

蛋白质与细胞

蛋白质与细胞

CSTPCD
影响因子：0.645
ISSN：
年,卷(期)：2024.15(1)
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