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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 418-429页

作者： Shuang LI Zhenzhen CHEN Chuanxin CHEN Yuyu Niu State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical Research Kunming 650500China Bioland Laboratory Guangzhou 510005China Guangzhou Laboratory Guangzhou 510005China

Efforts have been made to establish various human pluripotent stem cell lines.However,such methods have not yet been duplicated in non-human primate cells.Here,we introduce a multiplexed single-cell sequencing technique to profile the molecular features of monkey pluripotent stem cells in published culture conditions.The results demonstrate suboptimized maintenance of pluripotency and show that the selected signaling pathways for resetting human stem cells can also be interpreted for establishing monkey cell lines.Overall,this work legitimates the translation of novel human cell line culture conditions to monkey cells and provides guidance for exploring chemical cocktails for monkey stem cell line derivation.

关键词： Monkey pluripotent stem cell Multiplexed single-cell sequencing Naive pluripotency Extended pluripotent stem cells

Genetic monkeys reveal a new role for a longevity protein in embryonic development

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National Science Review 2019年第3期6卷 392-392页

作者： Yuyu Niu Yunnan Key Laboratory of Primate Biomedicine Research Institute of Primate Translational Medicine Kunming University of Science and Technology

As it is involved in boosting lifespan in mammals, SIRT6 has been in the spotlight for years. In mice, SIRT6 overexpression leads to improved health and lifespan extension [1]. Animals die soon after birth if SIRT-6 is deficient [2].A recent study in humans showed that SIRT6 mutation causes abnormal brain development and results in embryonic death [3]. This suggested that SIRT6 may play a different role in primate development. In a recent study published in Nature, a team of Chinese Academy of

关键词： Genetic monkeys reveal a new role for a longevity protein in embryonic development

Paving the road for biomedicine: genome editing and stem cells in primates

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National Science Review 2017年第4期4卷 543-549页

作者： Yuyu Niu Tianqing Li Weizhi Ji Yunnan Key Laboratory of Primate Biomedicine Research Institute of Primate Translational Medicine Kunming University of Science and Technology

Non-human primates(NHPs) are similar with humans in their anatomy, physiology, genetics and neural functions, and in their cognition, emotions and social behavior. The NHP model has played an important role in the biomedical research, development of vaccines and drugs and new therapies for many diseases.Recent advances in genome editing have generated NHP models for human diseases. Genome editing integrated with derivation of NHP pluripotent stem cells now provides an optimal resource to regenerate medicine.

关键词： genome editing stem cells non-human primate

Recent advances in CRISPR research

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Protein & Cell 2020年第11期11卷 786-791页

作者： Baohui Chen Yuyu Niu Haoyi Wang Kejian Wang Hui Yang Wei Li Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Yunnan Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Rice Biology China National Rice Research InstituteChinese Academy of Agricultural SciencesHangzhou 310006China Institute of Neuroscience State Key Laboratory of NeuroscienceKey Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyShanghai Research Center for Brain Science and Brain-Inspired IntelligenceShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China

The clustered regularly interspaced short palindromic repeats(CRISPR)technology has revolutionized life sciences and developed rapidly.Here,we highlight the recent advances in development and application of CRISPR technologies,including the discovery of novel CRISPR systems,CRISPR base editing and imaging,and the applications of CRISPR in plant breeding,animal breeding,disease modeling and biotherapy.

关键词： CRISPR breeding advances

Long-read sequencing and de novo assembly of the cynomolgus macaque genome

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Journal of Genetics and Genomics 2022年第10期49卷 975-978页

作者： Bing Bai Yi Wang Ran Zhu Yaolei Zhang Hong Wang Guangyi Fan Xin Liu Hong Shi Yuyu Niu Weizhi Ji State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China Yunnan Key Laboratory of Primate Biomedical Research KunmingYunnan 650500China BGI-Qingdao BGI-ShenzhenQingdaoShandong 266555China Translational Immunology Group Department of Biotechnology and BiomedicineTechnical University of DenmarkLyngbyDenmark State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnnan 650500China BGI-Shenzhen ShenzhenGuangdong 518083China China National GeneBank BGI-ShenzhenShenzhenGuangdong 518120China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunmingYunnan 650500China Ji1 2

Cynomolgus macaques(Macaca fascicularis)belong to the genus Macaca.They are the most widespread nonhuman primate(NHP)and share a common ancestor with humans from about 25 million years ago(Kumar and Hedges,1998).Because of their phylogenetic proximity to humans,macaques are an attractive NHP research model for a wide range of biomedical research(Yan et al.,2011).

关键词： widespread attractive proximity

Interspecies embryo transfer between rhesus and cynomolgus monkeys

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Journal of Genetics and Genomics 2020年第6期47卷 333-336页

作者： Ting Zhang Yu Kang Li Li Yin Zhou Xinglong Chen Yan Zhuo Zifan Li Hong Wang Yuyu Niu Weizhi Ji Shangang Li Yongchang Chen Yunnan Key Laboratory of Primate Biomedicine Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming650500China Faculty of Environmental Science and Engineering Kunming University of Science and TechnologyKunming650500China Department of Pediatrics The First People's Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and TechnologyKunming650032China

Nonhuman primates(NHPs)present significant advantages over rodents for physiological and pharmacological investigations because of their higher genetic and physiological similarity to humans.

关键词： primates transfer similarity

Current state of stem cell research in non-human primates:an overview

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Medical Review

Medical Review 2023年第4期3卷 277-304页

作者： Junmo Wu Yuxi Shi Shanshan Yang Zengli Tang Zifan Li Zhuoyao Li Jiawei Zuo Weizhi Ji Yuyu Niu Kunming University of Science and Technology KunmingYunnan ProvinceChina Yunnan Key Laboratory of Primate Biomedical Research KunmingYunnan ProvinceChina

The remarkable similarity between non-human primates(NHPs)and humans establishes them as essential models for understanding human biology and diseases,as well as for developing novel therapeutic strategies,thereby providing more comprehensive reference data for clinical treatment.Pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells provide unprecedented opportunities for cell therapies against intractable diseases and injuries.As continue to harness the potential of these biotechnological therapies,NHPs are increasingly being employed in preclinical trials,serving as a pivotal tool to evaluate the safety and efficacy of these interventions.Here,we review the recent advancements in the fundamental research of stem cells and the progress made in studies involving NHPs.

关键词： non-human primates cell therapy stem cell

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基于异质注意力循环神经网络的文本推荐

计算机工程 2020年第10期46卷 52-59页

作者：牛耀强孟昱煜牛全福兰州交通大学电子与信息工程学院兰州730070 兰州理工大学土木工程学院兰州730050

针对当前大数据环境下文本推荐不精确的问题,对文本数据和关系网络2种异质数据进行融合,并引入编码器-解码器框架,提出基于异质注意力的循环神经网络模型用于短期文本推荐。使用句子级的分布记忆模型和实体关系表示方法TransR,分别将文... 详细信息

针对当前大数据环境下文本推荐不精确的问题,对文本数据和关系网络2种异质数据进行融合,并引入编码器-解码器框架,提出基于异质注意力的循环神经网络模型用于短期文本推荐。使用句子级的分布记忆模型和实体关系表示方法TransR,分别将文本数据和关系网络嵌入到高维向量中作为模型的输入。在编码器阶段,使用双向GRU将用户的短期兴趣引入到推荐模型中,并将注意力机制与解码器相连接,使解码器能动态地选择并线性组合编码器输入序列的不同部分,以建模用户在短期内的偏好。在解码器阶段,将编码器的注意力输出、候选项和当前用户的表示作为输入。通过双向GRU和前馈网络层,计算每个候选项的得分得到推荐结果。实验结果表明,与TF-IDF和ItemKNN等模型相比,该模型在召回率和均值平均精度指标上均有明显提升。

关键词：短期文本推荐数据嵌入异质数据双向GRU 注意力机制

Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing

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Protein & Cell 2020年第11期11卷 809-824页

作者： Fang Wang Weiqi Zhang Qiaoyan Yang Yu Kang Yanling Fan Jingkuan Wei Zunpeng Liu Shaoxing Dai Hao Li Zifan Li Lizhu Xu Chu Chu Jing Qu Chenyang Si Weizhi Ji Guang-Hui Liu Chengzu Long Yuyu Niu Yunnan Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China The Leon H Charney Division of Cardiology New York University School of MedicineNew YorkNY 10016USA State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Department of Neuroscience and Physiology New York University School of MedicineNew YorkNY 10016USA Department of Neurology New York University School of MedicineNew YorkNY 10016USA

Many human genetic diseases,including Hutchinson-Gilford progeria syndrome(HGPS),are caused by single point mutations.HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene.Base editors(BEs)composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions.Here,we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA(gRNA)targeting the LMNA gene via microinjection into monkey zygotes.Five out of six newborn monkeys carried the mutation specifically at the target site.HGPS monkeys expressed the toxic form of lamin A,progerin,and recapitulated the typical HGPS phenotypes including growth retardation,bone alterations,and vascular abnormalities.Thus,this monkey model genetically and clinically mimics HGPS in humans,demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.

关键词： base editing non-human primate HGPS

Long-term in vivo chimeric cells tracking in non-human primate

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Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang Xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical Research Kunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates