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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 *** 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

PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis

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Protein & Cell 2022年第1期13卷 26-46页

作者： Weili Yang Xiangyu Guo Zhuchi Tu Xiusheng Chen Rui Han Yanting Liu Sen Yan Qi Wang Zhifu Wang Xianxian Zhao Yunpeng Zhang Xin Xiong Huiming Yang Peng Yin Huida Wan Xingxing Chen Jifeng Guo Xiao-Xin Yan Lujian Liao Shihua Li Xiao-Jiang Li guangdong key laboratory of non-human primate research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhou 510632China key laboratory of Brain Functional Genomics of Ministry of Education Shanghai Key Laboratory of Brain Functional Genomicsand Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai 100021China Department of Neurology Xiangya HospitalCentral South UniversityChangsha 410008China Department of Anatomy and Neurobiology Xiangya School of MedicineCentral South UniversityChangsha 410008China

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease(PD).However,difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of *** we report that PINK1 kinase form is selectively expressed in the human and monkey ***/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and ***,PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and *** findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

关键词： Parkinson's disease neurogenesis neurodegeneration mitochondria non-human primates

Brain developmental and cortical connectivity changes in transgenic monkeys carrying the human-specific duplicated gene SRGAP2C

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National Science Review 2023年第11期10卷 45-60页

作者： Xiaoyu Meng Qiang Lin Xuerui Zeng Jin Jiang Min Li Xin Luo Kaimin Chen Haixu Wu Yan Hu Cirong Liu Bing Su State key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences National Resource Center for non-human primates Kunming Primate Research Centerand National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility)Kunming Institute of ZoologyChinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Center for Excellence in Brain Science and Intelligence Technology Institute of NeuroscienceCAS Key Laboratory of Primate NeurobiologyChinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

human-specific duplicated genes contributed to phenotypic innovations during the origin of our own species, such as an enlarged brain and highly developed cognitive abilities. While prior studies on transgenic mice carrying the human-specific SRGAP2C gene have shown enhanced brain connectivity, the relevance to humans remains unclear due to the significant evolutionary gap between humans and rodents. In this study,to investigate the phenotypic outcome and underlying genetic mechanism of SRGAP2C, we generated transgenic cynomolgus macaques(Macaca fascicularis) carrying the human-specific SRGAP2C *** MRI imaging revealed delayed brain development with region-specific volume changes,accompanied by altered myelination levels in the temporal and occipital regions. On a cellular level, the transgenic monkeys exhibited increased deep-layer neurons during fetal neurogenesis and delayed synaptic maturation in adolescence. Moreover, transcriptome analysis detected neotenic expression in molecular pathways related to neuron ensheathment, synaptic connections, extracellular matrix and energy metabolism. Cognitively, the transgenic monkeys demonstrated improved motor planning and execution skills. Together, our findings provide new insights into the mechanisms by which the newly evolved gene shapes the unique development and circuitry of the human brain.

关键词： SRGAP2C transgenic monkey brain evolution brain development neurogenesis neoteny

TBtools-II: A “one for all, all for one” bioinformatics platform for biological big-data mining

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Molecular Plant 2023年第11期16卷 1733-1742页

作者： Chengjie Chen Ya Wu Jiawei Li Xiao Wang Zaohai Zeng Jing Xu Yuanlong Liu Junting Feng Hao Chen Yehua He Rui Xia State key laboratory for Conservation and Utilization of Subtropical Agro-Bioresources College of HorticultureSouth China Agricultural UniversityGuangzhouGuangdong 510640China key laboratory of Biology and Germplasm Enhancement of Horticultural Crops in South China Ministry of Agriculture and Rural AffairSouth China Agricultural UniversityGuangzhouGuangdong 510640China guangdong laboratory for Lingnan Modern Agriculture South China Agricultural UniversityGuangzhouGuangdong 510640China guangdong key laboratory of non-human primate research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China State key laboratory of Crop Stress Adaptation and Improvement Henan Joint International Laboratory for Crop Multi-Omics ResearchSchool of Life SciencesHenan UniversityKaifeng 475004China key laboratory of Genetic Improvement of Bananas Sanya Research InstituteState Key Laboratory of Tropical Crop BreedingInstitute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural SciencesHaikouHainan 571101China College of Agronomy Hunan Agricultural UniversityChangsha 410128China

Since the official release of the stand-alone bioinformatics toolkit TBtools in 2020,its superior functionality in data analysis has been demonstrated by its widespread adoption by many thousands of users and references in more than 5000 academic ***,TBtools is a commonly used tool in biological *** the past 3 years,thanks to invaluable feedback and suggestions from numerous users,we have optimized and expanded the functionality of the toolkit,leading to the development of an upgraded version—*** this upgrade,we have incorporated over 100 new features,such as those for comparative genomics analysis,phylogenetic analysis,and data ***,to better meet the increasing needs of personalized data analysis,we have launched the plugin mode,which enables users to develop their own plugins and manage their selection,installation,and removal according to individual *** date,the plugin store has amassed over 50 plugins,with more than half of them being independently developed and contributed by TBtools *** plugins offer a range of data analysis options including co-expression network analysis,single-cell data analysis,and bulked segregant analysis sequencing data ***,TBtools is now transforming from a stand-alone software to a comprehensive bioinformatics platform of a vibrant and cooperative community in which users are also developers and *** promoting the theme“one for all,all for one”,we believe that TBtools-II will greatly benefit more biological researchers in this big-data era.

关键词： TBtools-ll plugin biological big data BSA-seq

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 ***,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical ***,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 ***,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in *** cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed *** also found expression of signaling pathways components that may increase the potential for chimera *** 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 *** engineered cells retained embryonic and extra-embryonic developmental ***,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living *** 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

Design methods for antimicrobial peptides with improved performance

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Zoological research 2023年第6期44卷 1095-1114页

作者： James Mwangi Peter Muiruri Kamau Rebecca Caroline Thuku Ren Lai key laboratory of Bioactive Peptides of Yunnan Province Engineering Laboratory of Peptides of Chinese Academy of SciencesKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Centre for Non-Human PrimatesKunming Primate Research CentreNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Sino-African Joint Research CentreNew Cornerstone Science InstituteKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China Centre for Evolution and Conservation Biology Southern Marine Science and Engineering Guangdong LaboratoryGuangzhouGuangdong 511458China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China

The recalcitrance of pathogens to traditional antibiotics has made treating and eradicating bacterial infections more *** this regard,developing new antimicrobial agents to combat antibiotic-resistant strains has become a top *** peptides(AMPs),a ubiquitous class of naturally occurring compounds with broadspectrum antipathogenic activity,hold significant promise as an effective solution to the current antimicrobial resistance(AMR)*** AMPs have been identified and evaluated for their therapeutic application,with many already in the drug development *** distinct properties,such as high target specificity,potency,and ability to bypass microbial resistance mechanisms,make AMPs a promising alternative to traditional ***,several challenges,such as high toxicity,lability to proteolytic degradation,low stability,poor pharmacokinetics,and high production costs,continue to hamper their clinical ***,recent research has focused on optimizing the properties of AMPs to improve their *** understanding the physicochemical properties of AMPs that correspond to their activity,such as amphipathicity,hydrophobicity,structural conformation,amino acid distribution,and composition,researchers can design AMPs with desired and improved *** this review,we highlight some of the key strategies used to optimize the performance of AMPs,including rational design and de novo *** also discuss the growing role of predictive computational tools,utilizing artificial intelligence and machine learning,in the design and synthesis of highly efficacious lead drug candidates.

关键词： Antimicrobial resistance Antimicrobial peptides Design methods Peptidomimetics Artificial intelligence

Establishing age-group specific reference intervals of human salivary proteome and its preliminary application for epilepsy diagnosis

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Science China Life Sciences 2025年第03期 809-824页

作者： Nianci Xue Xia Xia Yini Wang Xianju Li Nairen Zheng Yi Wang Baoying Gong Bin Zhang Yanjia Chen Yue Chen Yanjuan Li Hong Cao Wofeng Liu Hongqiang Huang Shuo Yang Lisen Sui Lin Meng Jianwen Guo Jun Qin State key laboratory of Traditional Chinese Medicine Syndrome State Key Laboratory of Dampness Syndrome of Chinese Medicine Syndrome Department of Neurology The Secondary Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine Guangdong Provincial Academy of Chinese Medical Sciences State key laboratory of Medical Proteomics Beijing Proteome Research Center National Center for Protein Sciences (Beijing) Beijing Institute of Lifeomics Guangzhou University of Chinese Medicine guangdong Mechanical & Electrical Polytechnic Department of epilepsy The Secondary Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Traditional Chinese Medicine Guangzhou Cadre and Talent Health Management Center (Guangzhou 11th People's Hospital)

Salivary proteins serve multifaceted roles in maintaining oral health and hold significant potential for diagnosing and monitoring diseases due to the non-invasive nature of saliva sampling. However, the clinical utility of current saliva biomarker studies is limited by the lack of reference intervals(RIs) to correctly interpret the testing result. Here, we developed a rapid and robust saliva proteome profiling workflow,obtaining coverage of >1,200 proteins from a 50-μL unstimulated salivary flow with 30 min gradients. With the workflow, we investigated protein variation in a cohort of 1,743 healthy individuals. The significant differences in non-linear saliva proteomes among age groups resulted in the establishment of age-related RIs covering 1,123 salivary protein variations. We then utilized a cohort of 30 epilepsy patients as a case study to illustrate the practical application of RIs in identifying disease-enriched outlier proteins, elucidating their cellular origins,determining disease diagnosis, and visualizing outlier proteins in each epilepsy patient. Our study showed the classification model based on the RI achieved PR-AUC of 0.815(95%CI: 0.813–0.826). Additionally, we validated these results in an independent test set. Furthermore, the epilepsy cohort could be further stratified into 2 major subtypes, with one subtype characterized by disrupted metabolic proteins and containing mostly Focal Cortical Dysplasia(FCD) type III epilepsy patients. Overall, our study provided a proof-of-principle workflow for the use of salivary proteome for health monitoring, epilepsy diagnosis and subtyping.

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A cynomolgus monkey with naturally occurring Parkinson's disease

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National Science Review 2021年第3期8卷 17-20页

作者： Hao Li Ling-Yan Su Lixin Yang Min Li Qianjin Liu Zhenhui Li Yan Hu Hongwei Li Shihao Wu Wenchao Wang Yingzhou Hu Zhengbo Wang Joshua D.Rizak Baihui Huang Min Xu Jing Wu Long-Bao Lv Christoph W.Turck Yong Yin Yong-Gang Yao Bing Su Xintian Hu key laboratory of Animal Models and human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences State key laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Shenzhen key laboratory for Molecular Biology of Neural Development Guangdong Provincial Key Laboratory of Brain Connectome and Behavior CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences China Kunming College of Life Science University of Chinese Academy of Sciences Institute of Neuroscience CAS Key Laboratory of Primate Neurobiology State Key Laboratory of NeuroscienceChinese Academy of Sciences National Resource Center for non-human primates Kunming Primate Research Center and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) Kunming Institute of Zoology Chinese Academy of Sciences Max Planck Institute of Psychiatry Department of Translational Research in Psychiatry Department of Rehabilitation Medicine the Second People’s Hospital of Yunnan Province Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences KIZ–CUHK Joint laboratory of Bioresources and Molecular research in Common Diseases Kunming Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

Evidence for the existence of monkeys with spontaneous Parkinson’s disease (PD) has been lacking. Here,we screened macaque colonies at the Kunming primate research Center(Association for Assessment and Accreditation of laboratory Animal Care(AAALAC) accredited), Kunming Institute of Zoology, Chinese Academy of Sciences, which has a large population of monkeys (>2400), to identify naturally occurring PD monkeys.

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Increased attention to snake images in cynomolgus monkeys: an eye-tracking study

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Zoological research 2020年第1期41卷 32-38页

作者： Bo Zhang Zhi-Gang Zhou Yin Zhou Yong-Chang Chen Guangxi key laboratory of Brain and Cognitive Neuroscience Guilin Medical UniversityGuilinGuangxi 541199China Yunnan key laboratory of primate Biomedicine research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China

Previous studies have revealed faster detection of snake images in humans and non-human primates(NHPs),suggesting automatic detection of evolutionary fear-relevant ***,human studies have indicated that general fear-relevance rather than evolutionary relevance is more effective at capturing ***,the issue remains unclarified in ***,in the present study,we explored the attentional features of laboratory-reared monkeys to evolutionary and general fear-relevant stimuli(e.g.,images of snakes,capturing gloves).Eye-tracking technology was utilized to assess attentional features as it can provide more accurate latency and variables of viewing duration and frequency compared with visual search task(VST)and response latency adopted in previous *** addition,those with autism spectrum disorder(ASD)show abnormal attention to threatening stimuli,including snake *** syndrome(RTT)is considered a subcategory of ASD due to the display of autistic ***,the attentional features of RTT patients or animal models to such stimuli remain ***,we also investigated the issue in MECP2 gene-edited RTT *** influence of different cognitive loads on attention was further explored by presenting one,two,or four images to increase stimulus *** eye-tracking results revealed no significant differences between RTT and control monkeys,who all presented increased viewing(duration and frequency)of snake images but not of aversive stimuli compared with control images,thus suggesting attentional preference for evolutionary rather than general fear-relevant visual ***,the preference was only revealed in visual tasks composed of two or four images,suggesting its cognitive-load dependency.

关键词： non-human primates Attention Snake Evolutionary relevance