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

Protein & cell 2024年第1期15卷 36-51页

作者： 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 Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing Institute for Stem cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

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 ***,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely ***,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-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 *** comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular *** found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic ***,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

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Integration of single-cell RNA sequencing and network disturbance to elucidate crosstalk between multi-components drug and trigeminal ganglia cells in migraine

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中国药理学与毒理学杂志 2023年第S1期37卷 38-39页

作者： ZHANG Bo XI Yujie HUANG Ying ZHANG Yi GUO Feifei YANG Hongjun Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Pre-vention and Treatment for Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijingChina China Academy of Chinese Medical Sciences Beijing 100700China

OBJECTIVE To clarify the mecha⁃nism of Tou Tong Ning capsule(TTNC)and elu⁃cidate crosstalk between multi-components drug and trigeminal ganglia cells in ***⁃ODS We integrated single-cell RNA sequencing data and a quantitative evaluation algorithm of the disturbance of multi-target drugs on the dis⁃ease network to explore the specific pathology of TTNC for *** smooth muscle spasmolytic activity experiment was car⁃ried out to verify the results of bioinformatics *** TTNC can effectively regu⁃late the functions of synaptic signaling,inflamma⁃tion and immune response,and cerebrovascular smooth *** different cell subtypes of tri⁃geminal ganglia,TTNC can significantly disturb the robustness on neuronal cell networks and non-neural networks(fibroblast and vascular cells),indicating TTNC vasodilation activity of brain vessels and neural regulation activities of various neuro *** of cerebrovas⁃cular smooth muscle of mouse ex vivo confirmed the vasodilation activity of TTNC and active com⁃pounds(Emodin,Luteolin and Levistilide A).And literature mining confirmed the vasospasmolytic activity and neuroprotective effect activity of *** Integrating single-cell data and network disturbance tools provides a new strategy for the MoA of multi-components drug through cell subtyping.

关键词： Tou Tong Ning capsule(TTNC) migraine ScRNA-sq network disturbance vascular cell

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