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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

Zoological Research 2024年第4期45卷 747-766页

作者： Hong-Yi Zheng Tian-Zhang Song Yong-Tang Zheng state key laboratory of genetic evolution&animal models KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole ***,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 *** among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of *** effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and *** animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

关键词： SARS-CoV-2 COVID-19 animal models Infection immunology Immunotherapy

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Generation of mitochondrial replacement monkeys by female pronucleus transfer

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Zoological Research 2024年第2期45卷 292-298页

作者： Chun-Yang Li Xing-Chen Liu Yu-Zhuo Li Yan Wang Yan-Hong Nie Yu-Ting Xu Xiao-Tong Zhang Yong Lu Qiang Sun Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China key laboratory of genetic evolution and animal models Chinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe *** replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA *** pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously *** this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear *** individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during *** successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

关键词： Non-human primates Mitochondrial replacement Female pronuclear transfer

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Zika virus infection induces glycometabolic disorder in northern pig-tailed macaques

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Science China Life Sciences 2024年

作者： Qing Li Ren-Hua Yang Yan Hu Bei-Bei Tang Ying-Jie Jiang Chang-Bo Zheng Tian-Zhang Song state key laboratory of genetic evolution&animal models Key Laboratory of Bioactive Peptides of Yunnan ProvinceKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences School of Pharmaceutical Science&Yunnan key laboratory of Pharmacology for Natural Products Kunming Medical University University of Chinese Academy of Sciences KIZ-SU Joint laboratory of animal Model and Drug Development College of Pharmaceutical SciencesSoochow University

Dear Editor,The Zika virus (ZIKV) was first identified in Africa in 1947 but remained relatively obscure for nearly 70 ***,from 2014 to 2016,ZIKV was introduced into Brazil from the Pacific Islands,leading to its rapid dissemination throughout the Americas (Fauci and Morens,2016).This mosquito-borne virus is distinguished by its capacity to cause congenital defects,as evidenced by the microcephaly epidemic in Brazil,and has been declared a Public Health Emergency of International Concern (Gulland,2016).

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Comparative transcriptome analysis between rhesus macaques(Macaca mulatta) and crab-eating macaques(M. fascicularis)

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Zoological Research 2024年第2期45卷 299-310页

作者： Yu-Xiang Mao Yamei Li Zikun Yang Ning Xu Shilong Zhang Xuankai Wang Xiangyu Yang Qiang Sun Yafei Mao Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science&Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology Shanghai 201210China University of Chinese Academy of Sciences Beijing 100049China key laboratory of genetic evolution&animal models Chinese Academy of SciencesKunmingYunnan 650201China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghai 200030China Zhiyuan College Shanghai Jiao Tong UniversityShanghai 200240China Center for Genomic Research International Institutes of MedicineFourth Affiliated HospitalZhejiang UniversityYiwuZhejiang 322000China

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.

关键词： Crab-eating macaques Rhesus macaques Comparative transcriptomics Biomedical models Nonhuman primates RNA-seq Duplicated genes

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Ancient mitochondrial genome depicts sheep maternal dispersal and migration in Eastern Asia

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Journal of genetics and Genomics 2024年第1期51卷 87-95页

作者： Liu Yang Xing Zhang Yaning Hu Piao Zhu Hua Li Zhenyu Peng Hai Xiang Xinying Zhou Xingbo Zhao National Engineering laboratory for animal Breeding Key Laboratory of AnimalGeneticsBreeding and ReproductionMinistry of Agriculture and Rural AffairsCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Guangdong Provincial key laboratory of animal Molecular Design and Precise Breeding School of Life Science and EngineeringFoshan UniversityFoshanGuangdong 528225China state key laboratory of Agricultural Genomics BGI-ShenzhenShenzhenGuangdong 518083China key laboratory of Vertebrate evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China

Sheep have been one of the most important groups of animals since ancient ***,the knowledge of their migration routes and genetic relationships is still poorly *** investigate sheep maternal migration histories alongside Eurasian communications routes,in this study,we obtain mitochondrial genomes(mitogenomes)from 17 sheep remains in 6 Chinese sites and 1 Uzbekistan site dated 4429–3100 years before present(BP).By obtaining the mitogenomes from the sheep(4429–3556 BP)found in the Tongtian Cave site in Xinjiang,Altai region of northwest China,our results support the emergence of haplogroup C sheep in Xinjiang as early as 4429–3556 *** combined phylogenetic analyses with extant ancient and modern sheep mitogenomes suggest that the Uzbekistan-Altai region may have been a migration hub for early sheep in eastern *** least two migration events have taken place for sheep crossing Eurasia to China,one passing by Uzbekistan and Northwest China to the middle and lower reaches of the Yellow River at approximately 4000 BP and another following the Altai region to middle Inner Mongolia from 4429 BP to 2500 ***,this study provides further evidence for early sheep utilization and migration patterns in Eastern Asia.

关键词： Sheep Ancient DNA Eastern Asia Mitochondrial genome Migration Altai

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Three-stage niobium mineralization at Bayan Obo, China

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National Science Review 2024年第4期11卷 102-110页

作者： Yan Yu Yang Li Yu Liu Xiao-Xiao Ling Li-Guang Wu Li Yang Lan Yang Bo Yang Yong-Gang Zhao Xian-Hua Li state key laboratory of Lithospheric evolution Institute of Geology and Geophysics Chinese Academy of Sciences College of Earth and Planetary Science University of Chinese Academy of Sciences Ministry of Education key laboratory of Orogenic Belts and Crustal evolution School of Earth and Space SciencesPeking University Mining Research Institute Baotou Iron and Steel(Group) Co.LTD state key laboratory of Baiyunobo Rare Earth Resource Research and Comprehensive Utilization

The Chinese Bayan Obo deposit is a world-class rare earth element(REE) deposit with considerable niobium(Nb) and iron(Fe) resources. A complete genetic understanding on all metals is fundamental for establishing genetic models at Bayan Obo. With extensive research being focused on REE enrichment, the timing and controls of Nb enrichment remain unresolved at Bayan Obo, which is mainly due to the challenges in dating, i.e. multistage thermal events, fine-grained minerals with complex textures and the rare occurrence of uranium-enriched minerals with mature dating methods. Based on robust geological and petrographic frameworks, here we conducted ion probe uranium-lead(U-Pb) dating of ferrocolumbite to unravel the timing, hence the genesis of Nb mineralization. Three types of hydrothermal ferrocolumbites—key Nb-bearing minerals—are identified based on their textures and mineral assemblages. They yield U-Pb ages of 1312 ± 47 Ma(n = 99), 438 ± 7 Ma(n = 93), and 268 ± 5 Ma(n = 19), respectively. In line with deposit geology, we tentatively link the first, second and third stage Nb mineralization to Mesoproterozoic carbonatite magmatism, ubiquitous early Paleozoic hydrothermal activity, and Permian granitic magmatism, respectively. While quantifying the contribution of metal endowment from each stage requires further investigation, our new dates highlight that multi-stage mineralization is critical for Nb enrichment at Bayan Obo, which may also have implications for the enrichment mechanism of Nb in REE deposits in general.

关键词： niobium mineralization U-Pb dating ferrocolumbite Bayan Obo

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Weakened tanning ability is an important mechanism for evolutionary skin lightening in East Asians

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Journal of genetics and Genomics 2024年第7期51卷 703-713页

作者： Youwei Pu Siyu Pu Yanyan Chen Qinghong Kong Xuyang Liu Qi Zhao Ke Xu Jiuming Liu Mengyuan Li Xiaoyu Xu Xiaoyang Qiao Bing Su Jing Chen Zhaohui Yang Tianjian laboratory of Advanced Biomedical Sciences Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450052China Department of Pediatric Surgery and laboratory of Pediatric Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Guizhou Provincial College-based key Lab for Tumor Prevention and Treatment with Distinctive Medicines Zunyi Medical UniversityZunyiGuizhou 563000China Yunnan key laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China state key laboratory of genetic Resources and evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Center for Excellence in animal evolution and genetics Chinese Academy of SciencesKunmingYunnan 650223China

The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude *** Asians are ideal populations for studying skin color evolution because of the complex environment of East ***,we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase(PAH)in light-skinned Han Chinese *** intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males(Pgenetic mechanism for evolutionary skin lightening in East Asians.

关键词： East Asians PAH Skin pigmentation Natural selection genetic adaptation

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A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science China(Life Sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao Lin-Lin Liu Jian Sun Lian Jin Hai-Bing Xie Jian-Bo Li Hui Xu Dong-Dong Wu Xiao-Lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-Jie Sun Liang-Hu Qu Jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping Zhang state key laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China key laboratory of animal models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China state key laboratory of genetic Resources and evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The key laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai key laboratory of Cell Engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Human-specific insertions play important roles in human phenotypes and *** we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome ***,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee *** have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in *** addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in *** of Insert-446 prevented cell proliferation and migration in cancer and normal *** results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B *** findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

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Characteristics of genetic basis copy number variation in production and adaptation traits of Chinese indigenous sheep

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Journal of genetics and Genomics 2024年第5期51卷 566-569页

作者： Meilin Jin Gang Liu Jian Lu Zhiqiang Chen Huihua Wang Taotao Li Caihong Wei state key laboratory of animal Biotech Breeding Institute of Animal SciencesChinese Academy of Agricultural Sciences(CAAS)Beijing 100193China College of animal Science and Technology China Agricultural UniversityBeijing100193China National animal Husbandry Service National Center of Preservation&Utilization of Animal Genetic ResourcesBeijing 100125China Glbizzia Biosciences Beijing 102629China

Copy number variations(CNVs)range in size from 50 base pairs(bp)to several megabases(Mb)and encompass various types of structural variations,such as insertions,deletions,duplications,and complex multiallelic events(MacDonald et al.,2014).These genomic alterations modulate phenotype by altering gene dosage and transcriptional regulation,and are key drivers of biological evolution and determinants of genetic diversity and phenotypic *** recent years,CNVs have been detected in the genomes of various livestock species(Yuan et al.,2021;Chen et al.,2022).Upadhyay et al.(2017)conducted a comprehensive analysis of CNV distribution in the European cattle genome and determined that the Kit gene is associated with color-sidedness in English longhorn *** study presented extensive genome-wide information on CNVs in wild,commercial,and local chicken breeds to gain an integrated understanding of the domestication process and exclusively identified the genes involved(Chen et al.,2022).

关键词： sided number dosage

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Innovative 3D Microfluidic Intestinal Organoid Model for Assessing Cadmium Bioavailability in Food: Implications for Enhanced Exposure Risk Assessment

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Food Science and Human Wellness 2024年

作者： Yan Li Wen Sun Qiao Wang Wan Shi Yu Chen Zhiyong Gong Xiao Guo Xin Liu Yongning Wu key laboratory of animal Biological Products & genetic Engineering Ministry of Agriculture and Rural Sinopharm animal Health Corporation Ltd. state key laboratory of Novel Vaccines for Emerging Infectious Diseases China National Biotec Group Company Limited key laboratory for Deep Processing of Major Grain and Oil (The Chinese Ministry of Education) College of Food Science and Engineering Wuhan Polytechnic University Department of Oncology Xiangya Hospital Central South University NHC key laboratory of Food Safety Risk Assessment China National Center for Food Safety Risk Assessment

Given the severe toxicity and widespread presence of cadmium (Cd) in staple foods such as rice， accurate dietary exposure assessments are imperative for public health. In vitro bioavailability is commonly used to adjust dietary exposure levels of risk factors; however， traditional planar Transwell models have limitations， such as cell dedifferentiation and lack of key intestinal components， necessitating a more physiologically relevant in vitro platform. This study introduces an innovative three-dimensional (3D) intestinal organoid model using a microfluidic chip to evaluate Cd bioavailability in food. Caco-2 cells were cultured on the chip to mimic small intestinal villi's 3D structure， mucus production， and absorption functions. The model's physiological relevance was thoroughly characterized， demonstrating the formation of a confluent epithelial monolayer with well-developed tight junctions (ZO-1)， high microvilli density (F-actin)， and significant mucus secretion (Alcian blue staining)， closely resembling the physiological intestinal epithelium. Fluorescent particle tracking confirmed its ability to simulate intestinal transport and diffusion. The Cd bioavailability in rice measured by the 3D intestinal organoid model (9.07% ± 0.21%) was comparable to the mouse model (12.82% ± 3.42%) but significantly lower than the Caco-2 monolayer model (26.97% ± 1.11%). This 3D intestinal organoid model provides a novel and reliable strategy for in vitro assessment of heavy metal bioavailability in food， with important implications for food safety and risk assessment.

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