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Omics Views of Mechanisms for Cell Fate Determination in Early Mammalian Development

Genomics, Proteomics & Bioinformatics 2023年第5期21卷 950-961页

作者： Lin-Fang Ju Heng-Ji Xu Yun-gui Yang Ying yang Sino-Danish College University of Chinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

During mammalian preimplantation development,a totipotent zygote undergoes several cell cleavages and two rounds of cell fate determination,ultimately forming a mature blastocyst.Along with compaction,the establishment of apicobasal cell polarity breaks the symmetry of an embryo and guides subsequent cell fate choice.Although the lineage segregation of the inner cell mass(ICM)and trophectoderm(TE)is the first symbol of cell differentiation,several molecules have been shown to bias the early cell fate through their inter-cellular variations at much earlier stages,including the 2-and 4-cell stages.The underlying mechanisms of early cell fate determination have long been an important research topic.In this review,we summarize the molecular events that occur during early embryogenesis,as well as the current understanding of their regulatory roles in cell fate decisions.Moreover,as powerful tools for early embryogenesis research,single-cell omics techniques have been applied to both mouse and human preimplantation embryos and have contributed to the discovery of cell fate regulators.Here,we summarize their applications in the research of preimplantation embryos,and provide new insights and perspectives on cell fate regulation.

关键词： Cell fate determination Cellular heterogeneity Cell polarity Single-cell omics Mammalian preimplantation embryo

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Endogenous DNA Damage and Repair Enzymes—A short summary of the scientific achievements of Tomas Lindahl,Nobel Laureate in Chemistry 2015

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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 122-125页

作者： Arne Klungland Yun-gui Yang Department of Microbiology Division of Diagnostics and InterventionInstitute of Clinical MedicineOslo University Hospital Department of Molecular Medicine Faculty of MedicineInstitute of Basic Medical SciencesUniversity of Oslo CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of Sciences

Tomas Lindahl completed his medical studies at Karolinska Institute in 1970.Yet,his work has always been dedicated to unraveling fundamental mechanisms of DNA decay and DNA repair.His research is characterized with groundbreaking discoveries on the instability of our genome,the identification of novel DNA repair activities,the characterization of DNA repair pathways,and the association to diseases,throughout his 40 years of scientific career.

关键词： DNA repair completed career instability decay dedicated summary Clare breaking

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Base-excision repair and beyond—A short summary attributed to scientific achievements of Tomas Lindahl, Nobel Prize Laureate in Chemistry 2015

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Science China(Life Sciences) 2016年第1期59卷 89-92页

作者： Shuangli Mi Arne Klungland Yun-gui Yang Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development CAS Center for Excellence in Molecular Cell Science Beijing Institute of Genomics Chinese Academy of Sciences Department of Microbiology Division of Diagnostics and Intervention Institute of Clinical Medicine Oslo University HospitalRikshospitalet Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo

Tomas Lindahl contributed his scientific career to unveiling fundamental mechanisms of DNA decay and repair.He made several ground-breaking discoveries on genome instability,novel DNA repair activities and pathways,and disease association.The 2015 Nobel Prize in Chemistry was awarded jointly to Tomas Lindahl,Paul Modrich and Aziz Sancar for their mechanistic studies of DNA repair.Their findings

关键词：碱基切除修复诺贝尔奖得主托马斯科学成果归结化学科学生涯修复机制

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Differential Transcriptomic Landscapes of SARS-CoV-2 Variants in Multiple Organs from Infected Rhesus Macaques

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 1014-1029页

作者： Tingfu Du Chunchun Gao Shuaiyao Lu Qianlan Liu yun yang Wenhai Yu Wenjie Li Yong Qiao Sun Cong Tang Junbin Wang Jiahong Gao Yong Zhang Fangyu Luo Ying yang Yun-gui Yang Xiaozhong Peng National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunming 650118China State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentCollege of Future TechnologyBeijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 100049China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)caused the persistent coronavirus disease 2019(COVID-19)pandemic,which has resulted in millions of deaths worldwide and brought an enormous public health and global economic burden.The recurring global wave of infections has been exacerbated by growing variants of SARS-CoV-2.In this study,the virological characteristics of the original SARS-CoV-2 strain and its variants of concern(VOCs;including Alpha,Beta,and Delta)in vitro,as well as differential transcriptomic landscapes in multiple organs(lung,right ventricle,blood,cerebral cortex,and cerebellum)from the infected rhesus macaques,were elucidated.The original strain of SARS-CoV-2 caused a stronger innate immune response in host cells,and its VOCs markedly increased the levels of subgenomic RNAs,such as N,Orf9b,Orf6,and Orf7ab,which are known as the innate immune antagonists and the inhibitors of antiviral factors.Intriguingly,the original SARS-CoV-2 strain and Alpha variant induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants did.Moreover,a hyperinflammatory state and active immune response were shown in the right ventricles of rhesus monkeys by the up-regulation of inflammation-and immune-related RNAs.Furthermore,peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected individuals.Collectively,these data provide insights into the pathogenesis of COVID-19 at the early stage of infection by the original SARS-CoV-2 strain and its VOCs.

关键词： SARS-CoV-2 Variant of concern Subgenomic RNA Rhesus macaque Transcriptome

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温带湿地植物生物量分配格局调控群落水平养分回收效率对氮磷添加的响应

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Journal of Plant Ecology 2021年第1期14卷 58-66页

作者： yun Zhang gui-Sheng yang Fu-Xi Shiu Rong Mao Key Laboratory of National Forestry Administration on Forest Ecosystem Protection and Restoration of Poyang Lake Watershed College of ForestryJiangxi Agricullural UniversityNanchang 330045China Wuyishanxipo Observation and Research Station of Forest Ecosystem Zixi 335300China Environment and Plant Protection Institute Chinese Academy of Tropical Agricultural ScienceHaikou 571101China

养分回收是植物养分利用策略的一个重要组成部分,但养分有效性的变化如何调控群落尺度上植物养分回收过程仍不清楚。在本研究中,我们提出两个科学问题:(1)叶片和茎养分回收过程对养分有效性增加的响应格局是不是一致?(2)群落尺度上养分... 详细信息

养分回收是植物养分利用策略的一个重要组成部分,但养分有效性的变化如何调控群落尺度上植物养分回收过程仍不清楚。在本研究中,我们提出两个科学问题:(1)叶片和茎养分回收过程对养分有效性增加的响应格局是不是一致?(2)群落尺度上养分富集引起的植物养分回收变化是受物种内养分回收可塑性的影响还是受物种组成变化的调控?本研究以中国东北草本植物占优势的温带湿地为研究对象,利用施肥实验调查了氮和磷添加3年后物种水平上植物地上部分生物量以及叶和茎养分回收的变化趋势,并评价了群落尺度上植物养分回收对3年养分添加的响应。对于植物叶和茎而言,氮和磷添加对养分回收效率(nutrient resorption efficiency)均没有影响,但降低了相应的养分回收度(nutrient resorption proficiency)o同样地,在群落水平上,植物氮和磷养分回收度也随着相应的养分添加而降低。而且,由于植物群落组成变化及其引起的叶茎比降低,氮添加显著降低群落尺度上植物氮和磷的养分回收效率。这些研究结果表明,温带湿地植物叶和茎养分回收过程对养分有效性增加的响应是一致的,而且养分富集引起的物种组成以及叶和茎生物量分配格局变化是驱动群落尺度上植物养分回收动态的重要因素。

关键词：叶茎比养分富集养分回收度养分利用策略物种组成

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Functional characterization of a low-density lipoprotein receptor in the lepidopteran model,Bombyx mori

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Insect Science 2022年第5期29卷 1262-1274页

作者： gui-yun Li Xiao-Jing Liu Gang-Qi Fang Jie yang Shuai Zhan Mu-Wang Li Jiangsu Key Laboratory of Sericultural Biology and Biotechnology School of BiotechnologyJiangsu University of Science and TechnologyZhenjiangJiangsuChina CAS Key Laboratory of Insect Developmental and Evolutionary Biology CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghaiChina The Key Laboratory of Silkworm and Mulberry Genetic Improvement Ministry of AgricultureSericultural Research InstituteChinese Academy of Agricultural SciencesZhenjiangJiangsuChina CAS Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijingChina

The growth and development of metabolous insects are mainly regulated by ecdysone and juvenile hormone.As a member of the low-density lipoprotein receptor(LDLR)family,megalin(mgl)is involved in the lipoprotein transport of cholesterol which is an essential precursor for the synthesis of ecdysone.Despite extensive studies in mammals,the function of mgl is still largely unknown in insects.In this study,we characterize the function of mgl in the silkworm Bombyx mori,the model species of Lepidoptera.We find that mgl is broadly present in the genomes of lepidopteran species and evolved with divergence between lepidopterans and Drosophila.The expression pattern suggests a ubiquitous role of mgl in the growth and development in the silkworm.We further perform clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9-based mutagenesis of Bmmgl and find that both the development and the silk production of the silkworm are seriously affected by the disruption of Bmmgl.Our results not only explore the function of mgl in Lepidoptera but also add to our understanding of how cholesterol metabolism is involved in the development of insects.

关键词： Bombyx mori cholesterol CRISPR/Cas9 development megalin silkworm

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Characteristics of N^(6)-methyladenosine Modification During Sexual Reproduction of Chlamydomonas reinhardtii

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Genomics, Proteomics & Bioinformatics 2023年第4期21卷 756-768页

作者： Ying Lv Fei Han Mengxia Liu Ting Zhang Guanshen Cui Jiaojiao Wang Ying yang Yun-gui Yang Wenqiang yang Photosynthesis Research Center Key Laboratory of PhotobiologyInstitute of BotanyChinese Academy of SciencesBeijing 100093China China National Botanical Garden Beijing 100093China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 100049China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Innovative Academy of Seed Design Chinese Academy of SciencesBeijing 100093China

The unicellular green alga Chlamydomonas reinhardtii(hereafter Chlamydomonas)possesses both plant and animal attributes,and it is an ideal model organism for studying fundamental processes such as photosynthesis,sexual reproduction,and life cycle.N^(6)-methyladenosine(m^(6)A)is the most prevalent mRNA modification,and it plays important roles during sexual reproduction in animals and plants.However,the pattern and function of m^(6)A modification during the sexual reproduction of Chlamydomonas remain unknown.Here,we performed transcriptome and methylated RNA immunoprecipitation sequencing(MeRIP-seq)analyses on six samples from different stages during sexual reproduction of the Chlamydomonas life cycle.The results show that m^(6)A modification frequently occurs at the main motif of DRAC(D=G/A/U,R=A/G)in Chlamydomonas mRNAs.Moreover,m^(6)A peaks in Chlamydomonas mRNAs are mainly enriched in the 30 untranslated regions(30 UTRs)and negatively correlated with the abundance of transcripts at each stage.In particular,there is a significant negative correlation between the expression levels and the m^(6)A levels of genes involved in the microtubule-associated pathway,indicating that m^(6)A modification influences the sexual reproduction and the life cycle of Chlamydomonas by regulating microtubule-based movement.In summary,our findings are the first to demonstrate the distribution and the functions of m^(6)A modification in Chlamydomonas mRNAs and provide new evolutionary insights into m^(6)A modification in the process of sexual reproduction in other plant organisms.

关键词： N6-methyladenosine m^(6)A sequencing Sexual reproduction Microtubule-associated pathway Photosynthesis Chlamydomonas reinhardtii

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Decipher biological significance of the novel epitranscriptomic marker N6-Methyadenosine(m6A) in RNA

Decipher biological significance of the novel epitranscripto...

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中国生物化学与分子生物学会第十一次会员代表大会暨201...

作者： Yun-gui Yang CAS Key Laboratory of Genomics and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences

The N6-methyladenosine(m6A)modification is one of the most frequently methylated nucleotides in eukaryotic mRNA,accounting for over 80%of all RNA base methylations and present in various species.Recently two independent studies combining m6A-immunoprecipitation with high throughput analysis revealed that the m6A modification tends to mainly occur in intragenic regions including coding sequences(CDS),stop codon flanking regions and 3’-UTR.The frequency was especially high in the 3’-end of CDS and the first quarter of the 3’-UTR,with an average of 1 m6A per 2000 ribonucleotides.The m6A modification occurs in highly conserved regions with the consensus sequence:RRACH(R=G or A;H=A,C or U).During the course of brain development a

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Epitranscriptomic 5-Methylcytosine Profile in PM_(2.5)-induced Mouse Pulmonary Fibrosis

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Genomics, Proteomics & Bioinformatics 2020年第1期18卷 41-51页

作者： Xiao Han Hanchen Liu Zezhong Zhang Wenlan yang Chunyan Wu Xueying Liu Fang Zhang Baofa Sun Yongliang Zhao guibin Jiang Yun-gui Yang Wenjun Ding College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentCollege of Future TechnologyBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Exposure of airborne particulate matter(PM)with an aerodynamic diameter less than 2.5μm(PM2.5)is epidemiologically associated with lung dysfunction and respiratory symptoms,including pulmonary fibrosis.However,whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood.Herein,using a PM2.5-induced pulmonary fibrosis mouse model,we found that PM2.5 exposure leads to aberrant mRNA5-methylcytosine(m5C)gain and loss in fibrotic lung tissues.Moreover,we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure.Several genes act as m5C gain-upregulated factors,probably critical for the development of PM2.5-induced fibrosis in mouse lungs.These genes,including Lcn2,Mmp9,Chi3l1,Adipoq,Atp5j2,Atp5l,Atpif1,Ndufb6,Fgr,Slc11 a1,and Tyrobp,are highly related to oxidative stress response,inflammatory responses,and immune system processes.Our study illustrates the first epitranscriptomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.

关键词： PM2.5 exposure mRNA m^5C Pulmonary fibrosis Inflammation Immune response

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The obesity-associated FTO regulates gene expression of adipogenic factors

The obesity-associated FTO regulates gene expression of adip...

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生命的分子机器及其调控网络——2012年全国生物化学与...

作者： Yun-gui Yang Genome Structure & Stability Group Disease Genomics and Individualized Medicine LaboratoryBeijing Institute of GenomicsChinese Academy of Science

Obesity is the most serious public health problem of the 21st century,with dramatically increasing prevalence in adults and children.The discovery of the fat mass and obesity-associated gene(FTO) as the first gene contributing to non-syndromic human obesity by genome-wide association studies has accelerated the research on novel obesity gene(s).We previously showed that FTO as a RNA demethylase oxidatively demethylates the ubiquitous m6A modification in mRNA in vitro and in vivo in a manner comparable to those of the other AlkB family

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