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SH2B1.Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in humans and Mice

research 2024年第3期2023卷 369-389页

作者： Xiujuan Du Yuhua Yan Juehua Yu Tailin Zhu Chu-Chung Huang Lingli Zhang Xingyue Shan Ren Li Yuan Dai Hui LV Xiao-Yong Zhang Jianfeng Feng Wei-Guang Li Qiang Luo Fei Li Developmental and Behavioral Pediatric Department Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children's Environmental HealthXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Developmental and Behavioral Pediatric Department Shanghai Xinhua Children's HospitalShanghai 200092China national Clinical {1. center for Aging and Medicine at Huashan Hospital Institute of Science and Technology for Brain-lnspired IntelligenceMinistry of Education-Key Laboratory of Computational Neuroscience and Brain-lnspired IntelligenceFudan UniversityShanghai 200433China State Key laboratory of Medical Neurobiology and {1. of Education Frontiers center for Brain science Institutes of Brain Science and Human Phenom InstituteFudan UniversityShanghai 200032China shanghai Key {1. of Brain Functional genomics(ministry of Education) School of Life SciencesEast China Normal UniversityShanghai 200062China Department of Rehabilitation Medicine Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China center for Experimental Studies and {1. The First Affliated Hospital of Kunming Medical UniversityKunming 650032China shanghai {1. center for Brain science and Brain-lnspired Intelligence Shanghai201210China Institute of Cognitive Neuroscience School of Psychology and Cognitive ScienceEast China Normal UniversityShanghai 200062China.

Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a {1.-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1. TUFM, ATP2A1. and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1.variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1.in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1.regulated molecular pathways revealed that Sh2b1.deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1.in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.

关键词： metabolism impaired reversed

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Current progress in epigenetic research for hepato-carcinomagenesis

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science China(Life sciences) 2009年第1期52卷 31-42页

作者： HUANG Jian national human genome research center at shanghai-ministry of science and technology to build a healthy and disease Ge-nomics laboratory,shanghai 201203,China 1. national human genome research center at shanghai-ministry of science and technology to build a healthy and disease genomics laboratory Shanghai 201203 China

Hepatocellular carcinoma is the main type of primary liver cancer,and also one of the most malignant *** present,the pathogenesis mechanisms of liver cancer are not entirely *** has been shown that inactivation of tumor suppressor genes and activation of oncogenes play a significant role in carcinogenesis,caused by the genetic and epigenetic *** the past,people generally thought that genetic mutation is a key event of tumor pathogenesis,and somatic mutation of tumor suppressor genes is in particular closely associated with *** deeper understanding of tumors in recent years,increasing evidence has shown that epigenetic silencing of those genes,as a result of aberrant hypermethylation of CpG islands in promoters and histone modification,is essential to carcinogenesis and *** term epigenetics refers to heritable changes in gene expression caused by regulation mechanisms,other than changes in the underlying DNA *** epigenetic processes include DNA methylation,genome imprinting,chromotin remodeling,histone modification and microRNA *** paper reviews recent epigenetics {1. progress in the hepatocellular carcinoma study,and tries to depict the relationships between hepatocellular carcinomagenesis and DNA methylation as well as microRNA regulation.

关键词： tumor heaptocellular carcinoma epigenetics DNA methylation microRNA

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A toolbox for genetic manipulation in intestinal Clostridium symbiosum

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Synthetic and Systems Biotechnology 2024年第1期9卷 43-54页

作者： Pengjie Yang Jinzhong Tian Lu Zhang Hui Zhang Gaohua Yang Yimeng Ren Jingyuan Fang Yang Gu Weihong Jiang CAS-Key laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai200032China University of Chinese Academy of sciences Beijing100049China Xianghu laboratory Hangzhou311231China NHC Key laboratory of Digestive {1.s Division of Gastroenterology and HepatologyShanghai Institute of Digestive DiseaseRenji HospitalSchool of MedicineShanghai Jiao Tong University145 Middle Shandong RoadShanghai200001China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen518120China The Wallenberg laboratory Department of Molecular and Clinical MedicineSahlgrenska AcademyUniversity of GothenburgBruna Straket 16Gothenburg41345Sweden

Gut microbes are closely related with human health,but remain much to *** symbiosum is a conditionally pathogenic human gut bacterium and regarded as a potential biomarker for early diagnosis of intestinal ***,the absence of an efficient toolbox that allows diverse genetic manipulations of this bacterium limits its in-depth ***,we obtained the complete genome sequence of *** ATCC 1.940,a representative strain of *** this basis,we further developed a series of genetic manipulation methods for this ***,following the identification of a functional replicon pBP1.in *** ATCC 1.940,a highly efficient conjugative DNA transfer method was established,enabling the rapid introduction of exogenous plasmids into ***,we constructed a dual-plasmid CRISPR/Cas1.a system for genome editing in this bacterium,reaching over 60% repression for most of the chosen genes as well as efficient deletion(>90%)of three target ***,this toolbox was used for the identification of crucial functional genes,involving growth,synthesis of important metabolites,and virulence of *** ATCC *** work has effectively established and optimized genome editing methods in intestinal ***,thereby providing strong support for further basic and application research in this bacterium.

关键词： Gut Clostridium symbiosum Toolbox Gene overexpression Gene deletion Gene regulation

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Versatile plant genome engineering using anti-CRISPR-Cas1.a systems

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science China Life sciences 2024年

作者： Yao He Shishi Liu Long Chen Dongkai Pu Zhaohui Zhong Tang Xu Qiurong Ren Chuan Dong Yawei Wang Danning Wang Xuelian Zheng Fengbiao Guo Tao Zhang Yiping Qi Yong Zhang Integrative science {1. of Germplasm Creation in Western China (Chongqing) science City Chongqing Key Laboratory of Tree Germplasm Innovation and Utilization School of Life Sciences Southwest University Department of Biotechnology School of Life Sciences and Technology Center for Informational Biology University of Electronic Science and Technology of China Sichuan Institute of Edible Fungi Sichuan Academy of Agricultural Sciences Jiangsu Key laboratory of Crop {1. and Molecular Breeding/Zhongshan Biological Breeding laboratory/Key laboratory of Plant Functional {1. of the ministry of Education College of AgricultureYangzhou University Jiangsu Co-Innovation center for Modern Production {1. of Grain Crops/Jiangsu Key laboratory of Crop Genetics and Physiology Yangzhou University Department of Respiratory and Critical Care Medicine Zhongnan Hospital of Wuhan University Key laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education and School of Pharmaceutical Sciences Wuhan University Department of Plant science and Landscape Architecture University of Maryland College Park 20742 Institute for Bioscience and Bio{1. research University of Maryland

CRISPR-Cas1.a genome engineering systems have been widely used in plant {1. and crop breeding. To date, the performance and use of anti-CRISPR-Cas1.a systems have not been fully established in plants. Here, we conduct in silico analysis to identify putative anti-CRISPR systems for Cas1.a. These putative anti-CRISPR proteins, along with known anti-CRISPR proteins, are assessed for their ability to inhibit Cas1.a cleavage activity in vivo and in planta. Among all anti-CRISPR proteins tested, AcrVA1.shows robust inhibition of Mb2Cas1.a and LbCas1.a in E. coli. Further tests show that AcrVA1.inhibits LbCas1.a mediated genome editing in rice protoplasts and stable transgenic lines. Impressively, co-expression of AcrVA1.mitigates off-target effects by CRISPR-LbCas1.a, as revealed by whole genome sequencing. In addition, transgenic plants expressing AcrVA1.exhibit different levels of inhibition to LbCas1.a mediated genome editing, representing a novel way of fine-tuning genome editing efficiency. By controlling temporal and spatial expression of AcrVA1. we show that inducible and tissue specific genome editing can be achieved in plants. Furthermore, we demonstrate that AcrVA1.also inhibits LbCas1.a-based CRISPR activation(CRISPRa) and based on this principle we build logic gates to turn on and off target genes in plant cells. Together, we have established an efficient anti-CRISPR-Cas1.a system in plants and demonstrate its versatile applications in mitigating off-target effects, finetuning genome editing efficiency, achieving spatial-temporal control of genome editing, and generating synthetic logic gates for controlling target gene expression in plant cells.

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Haplotype-based phylogenetic analysis and population genomics uncover the origin and domestication of sweetpotato

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Molecular Plant 2024年第2期17卷 277-296页

作者： Mengxiao Yan Ming Li Yunze Wang Xinyi Wang M-Hossein Moeinzadeh Dora G.Quispe-Huamanquispe Weijuan Fan Yijie Fang Yuqin Wang Haozhen Nie Zhangying Wang Aiko Tanaka Bettina Heider Jan F.Kreuze Godelieve Gheysen Hongxia Wang Martin Vingron Ralph Bock Jun Yang shanghai Key {1. of Plant Functional genomics and Resources Shanghai Chenshan Botanical GardenShanghai 201602China College of Life sciences Chongqing Normal UniversityChongqing 401331China Biotechnology and Nuclear technology research Institute Sichuan Academy of Agricultural SciencesChengdu 610061China College of Life sciences Shanghai Normal UniversityShanghai 200234China Department of Computational Molecular Biology Max Planck Institute for Molecular GeneticsIhnestraBe 63-7314195 BerlinGermany Department of Biotechnology Ghent University9000 GhentBelgium Guangdong Provincial Key laboratory of Crops Genetics and Improvement Crop Research InstituteGuangdong Academy of Agricultural SciencesGuangzhou 510640China Graduate School of Bioagricultural sciences Nagoya UniversityChikusaNagoya 464-8601Japan international Potato {1.(CIP) LimaPeru CAS center for Excellence of Molecular Plant {1.s Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200233China Max-Planck-Institut fur Molekulare Pflanzenphysiologie Am Muhlenberg 114476 Potsdam-GolmGermany

The hexaploid sweetpotato(lpomoea batatas)is one of the most important root crops ***,its genetic origin remains controversial,and its domestication history remains *** this study,we used a range of genetic evidence and a newly developed haplotype-based phylogenetic analysis to identify two probable progenitors of *** diploid progenitor was likely closely related to lpomoea ae-quatoriensis and contributed the B,subgenome,IbT-DNA2,and the lineage 1.type of chloroplast genome to *** tetraploid progenitor of sweetpotato was most likely *** 4x,which donated the B2 subgenome,IbT-DNA1.and the lineage 2 type of chloroplast *** most likely originated from reciprocal crosses between the diploid and tetraploid progenitors,followed by a subsequent whole-genome *** addition,we detected biased gene exchanges between the subgenomes;the rate of B,to B2 subgenome conversions was nearly three times higher than that of B2 to B subgenome *** analyses revealed that genes involved in storage root formation,maintenance of genome stabil-ity,biotic resistance,sugar transport,and potassium uptake were selected during the speciation and domestication of *** study sheds light on the evolution of sweetpotato and paves the way forimprovementofthiscrop.

关键词： sweetpotato origin gene conversion domestication IbT-DNA HPA

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Current research status of immunology in the genomic era

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science China(Life sciences) 2009年第1期52卷 43-49页

作者： LI HaoWen1,LI JinZhi1,ZHAO GuoPing2 & WANG Ying1,2 1 shanghai Institute of Immunology,Institute of Medical science,shanghai Jiaotong University School of Medicine,shanghai 200025,China 2 shanghai-MOST Key laboratory of Health and disease genomics,Chinese national human genome center,shanghai 201203,China 1. shanghai Institute of Immunology Institute of Medical Science Shanghai Jiaotong University School of Medicine Shanghai 200025 China 2. shanghai-MOST Key {1. of Health and disease genomics Chinese National Human Genome Center Shanghai 201203 China

This review updates the current status of immunology research under the influence of {1.,both conceptually and *** particularly highlights the advantages of employing the high-throughput and large-scale technology,the large genomic database,and bioinformatic power in the immunology *** fast development in the fields of basic immunology,clinical immunology(tumor and infectious immunology) and vaccine designing is illustrated with respect to the successful usage of genomic *** also speculate the future research directions of immunology in the era of {1. and post-{1..

关键词： genomics immunology clinical immunology vaccine design

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Perspectives of DNA microarray and next-generation DNA sequencing technologies

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science China(Life sciences) 2009年第1期52卷 7-16页

作者： TENG XiaoKun1 & XIAO HuaSheng1,2 1 national Engineering center for Biochip at shanghai,shanghai 201203,China 2 shanghai-MOST Key laboratory of Health and disease genomics,Chinese national human genome center,shanghai 201203,China national Engineering {1. for Biochip at shanghai Shanghai 201203 China shanghai-MOST Key {1. of Health and disease genomics Chinese National Human Genome Center Shanghai 201203 China

DNA microarray and next-generation DNA sequencing technologies are important tools for high-throughput genome {1.,in revealing both the structural and functional characteristics of *** the past decade the DNA microarray technologies have been widely applied in the studies of functional genomics,systems biology and *** next-generation DNA sequencing method was first introduced by the 454 Company in 2003,immediately followed by the establishment of the Solexa and Solid techniques by other biotech *** it has not been long since the first emergence of this technology,with the fast and impressive improvement,the application of this technology has extended to almost all fields of genomics {1.,as a rival challenging the existing DNA microarray *** paper briefly reviews the working principles of these two technologies as well as their application and perspectives in genome {1..

关键词： DNA microarray next generation DNA sequencing genome

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Fine genetic mapping of the chromosome 1.q23.3 region in a Han Chinese population:insights into the apolipoprotein genes underlying the blood lipid-lipoprotein variances

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Journal of Genetics and genomics 2020年第12期47卷 756-769页

作者： Weihua Shou Chenhui Zhang Jinxiu Shi Hong Wu Wei Huan Department of Genetics Shanghai-MOST Key Laboratory of Health and Disease GenomicsChinese National Human Genome Center at Shanghai and Shanghai Academy of Science and TechnologyShanghai 200025China Department of Cardiology Changhai HospitalThe Second Military Medical UniversityShanghai 200433China

The unusual chromosome 1.q23.3 harboring the apolipoprotein(APO)gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular ***,its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well *** conducted a study for this target region in a Han Chinese population through a stepwise forward framework based on massive parallel sequencing,association analyses,genetic fine mapping,and functional *** present study identified new meaningful genetic associations that were not simply determined by statistical *** addition to the APOA5 gene,we found robust evidence of the genetic commitments of APOC3 and APOA1.to blood *** variants with high confidence were prioritized along with the potential biological mechanism interpretations in the wake of adaptive fine-mapping ***28491.4 in the APOC3 enhancer was discovered with an unrivaled posterior probability of causality for triglyceride levels and could mediate APOC3 expression through enhancer activity modulated by a combination of histone modifications and transcription factor ***,multiple lines of evidence converged in favor of rs3741.97 as a causal variant influencing high-density lipoprotein *** findings provided novel insights into this genomic locus in the Chinese population.

关键词： APO gene cluster Blood lipids Coronary artery disease Genetic associations Progressive analyses for prioritizing Causal genetic factors

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This work was supported by the European research Council Advanced Grant(ETAP-742985 to *** J.F.)and by the {1. of science and technology(grant 1.0-2636-B-005-001.to K.-J.L.).

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Plant Communications 2024年第1期5卷 130-147页

作者： Yu Zhang Yuan Fu Wenfei Xian Xiuli Li Yong Feng Fengjiao Bu Yan Shi Shiyu Chen Robin van Velzen Kai Battenberg Alison M.Berry Marco G.Salgado Hui Liu Tingshuang Yi Pascale Fournier Nicole Alloisio Petar Pujic Hasna Boubakri M.Eric Schranz Pierre-Marc Delaux Gane Ka-Shu Wong Valerie Hocher Sergio Svistoonoff Hassen Gherbi Ertao Wang Wouter Kohlen Luis G.Wall Martin Parniske Katharina Pawlowski Philippe Normand Jeffrey J.Doyle Shifeng Cheng Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518124China Biosystematics Group Department of Plant SciencesWageningen University6708PB Wageningenthe Netherlands Department of Plant sciences University of CaliforniaDavisDavisCA 95616USA Department of Ecology Environment and Plant SciencesStockholm University10691 StockholmSweden Germplasm Bank of Wild Species Kunming Institute of BotanyChinese Academy of SciencesLanhei RoadKunming 650201China Universite´de Lyon Universite´Lyon 1CNRSUMR5557Ecologie MicrobienneINRAUMR 141843 bd du 11 novembre 191869622 VilleurbanneFrance Laboratoire de Recherche en sciences Ve´ge´tales(LRSV) Universite´de ToulouseCNRSUPS24 chemin de Borde RougeAuzevilleBP4261731326 Castanet TolosanFrance Department of Biological sciences University of AlbertaEdmontonAB T6G 2E9Canada French national {1. Institute for Sustainable Development(IRD) UMR LSTM(IRD/CIRAD/INRAe/Montpellier University/Supagro)-Campus International BaillarguetTA A-82/J34398 Montpellier Cedex 5France national Key {1. of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologySIBSChinese Academy of SciencesShanghaiChina laboratory of Molecular Biology Department of Plant SciencesWageningen University6708PB Wageningenthe Netherlands laboratory of Biochemistry Microbiology and Soil Biological InteractionsDepartment of Science and TechnologyNational University of QuilmesCONICETBernalArgentina Faculty of Biology GeneticsLMU MunichGroßhaderner Strasse 2-482152 MartinsriedGermany School of Integrative Plant science Sections of Plant Biology and Plant Breeding&GeneticsCornell UniversityIthacaNY 14853USA State Key laboratory of Systematic and Evolutionary Botany Institute of BotanyChinese Academy of SciencesBeijing 100093China Univer

Plant root-nodule symbiosis(RNS)with mutualistic nitrogen-fixing bacteria is restricted to a single clade of angiosperms,the Nitrogen-Fixing Nodulation Clade(NFNC),and is best understood in the legume *** species share many commonalities,explained either by divergence from a common ancestor over 1.0 million years ago or by convergence following independent origins over that same time ***,comparative analyses of diverse nodulation syndromes can provide insights into constraints on nodulation—what must be acquired or cannot be lost for a functional symbiosis—and the latitude for Plant Communications Genomic landscape of nodulation variation in the ***,much remains to be learned about nodulation,especially outside of ***,we employed a large-scale phylogenomic analysis across 88 species,complemented by 1.1.RNA-seq libraries,to elucidate the evolution of *** phylogenomic analyses further emphasize the uniqueness of the transcription factor NIN as a master regulator of nodulation and identify key muta-tions that affect its function across the *** transcriptomic assessment revealed nodule-specific upregulated genes across diverse nodulating plants,while also identifying nodule-specific and nitrogen-response *** 70%of symbiosis-related genes are highly conserved in the four representative species,whereas defense-related and host-range restriction genes tend to be lineage *** study also identified over 900000 conserved non-coding elements(CNEs),over 300000 of which are unique to sampled NFNC ***-specific CNEs are enriched with the active H3K9ac mark and are correlated with accessible chromatin regions,thus representing a pool of candidate regula-tory elements for genes involved in ***,our results provide novel insights into the evolution of nodulation and lay a foundation for engineering of RNS traits in agriculturally important crops.

关键词： nitrogen-fixing root-nodule symbiosis two competing hypotheses phylogenomics phylotranscrip-tomics conserved non-coding elements convergence deep homology

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Learn to fight from the war

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Chinese science Bulletin 2009年第13期54卷 2157-2158页

作者： ZHAO GuoPing shanghai-MOST Key laboratory for disease and Health genomics,Chinese national human genome center at shanghai,shanghai 201203,China Lab of Synthetic Biology,shanghai Institutes of Biological sciences,Chinese Academy of sciences,shanghai 200031,China national Engineering research center for Biochip technology,shanghai Biochip Co.Ltd.,shanghai 201203,China School of Life sciences,Fudan University,shanghai 200433,China ZHONG Yang School of Life sciences,Fudan University,shanghai 200433,China shanghai center for Bioinformation technology,shanghai 200235,China shanghai-MOST Key {1. for disease and Health genomics Chinese National Human Genome Center at Shanghai Shanghai 201203 China Lab of Synthetic Biology Shanghai Institutes of Biological Sciences Chinese Academy of Sciences Shanghai 200031 China national Engineering {1. center for Biochip technology Shanghai Biochip Co. Ltd. Shanghai 201203 China School of Life sciences Fudan University Shanghai 200433 China shanghai {1. for Bioinformation technology Shanghai 200235 China

In March 2009,a novel type A (H1.1. influenza broke out in North America and rapidly spread all over the world.

关键词：世界卫生组织战争军备竞赛 WHO 流感

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