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SENP1 regulates IFN-γ-STAT1 signaling throug STAT3-SOCS3 negative feedback loop

Journal of Molecular cell biology 2017年第2期9卷 144-153页

作者： Tingting Yu Yong Zuo Rong Cai Xian Huang Shuai wu Chenxi Zhang Y. Eugene Chin Dongdong Li Zhenning Zhang Nansong Xia Qi wang Hao Shen Xuebiao Yao zhong-Yin Zhang Song Xue Lei Shen Jinke cheng Department of biochemistry and Molecular cell biology Shanghai Key Laboratory for Tumor Microenvironment and Inflammation Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Key Laboratory of cell Differentiation and Apoptosis of chinese Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Developmental Genetics School of Basic Medical Sciences Nanjing Medical University Nanjing 211166 China shanghai institute of Immunology Shanghai Jiao Tong University School of Medicine Shanghai 200025 China institute of Health sciences Chinese Academy of Sciences Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Microbiology University of Pennsylvania Perelman School of Medicine Philadelphia PA 19104 USA Anhui Key Laboratory of cellular Dynamics Hefei National Laboratory for Physical Sciences at Nanoscale University of Science and Technology of ChinaHefei 230026 China Department of biochemistry and Molecular biology Indiana University School of Medicine Indianapolis IN 46202 USA shanghai Renji Hospital Affiliated to shanghai Jiao Tong University School of Medicine Shanghai 200127 China

Interferon-γ （IFN-γ） triggers macrophage for inflammation response by activating the intracellular JAK-STAT1 signaling. Suppressor of cytokine signaling 1 （SOCS1） and protein tyrosine phosphatases can negatively modulate IFN-γ signaling. Here, we identify a novel negative feedback loop mediated by STAT3-SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B （PTPIB）, in IFN-y signaling. SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation. PTP1B in SENP1-deficient macrophages is highly SUMOylated, which reduces PTP1B-induced de-phosphorylation of STAT3. Activated STAT3 then suppresses STAT1 activation via SOCS3 induction in SENP1-deficient macro- phages. Accordingly, SENP1-deficient macrophages show reduced ability to resist Listerio rnonocytogenes infection. These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in rnacrophage polarization.

关键词： IFN-γ macrophage SENP1 SUMOylation

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Multi-valent mRNA vaccines against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity

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中国科学:生命科学英文版 2023年第10期66卷 2329-2341页

作者： Niubing Zhang Xiang cheng Yilong Zhu Ouyang Mo Huiqing Yu Liqi Zhu Juan Zhang Linlin Kuang Ying Gao Ruiyuan Cao Xiaozhen Liang Haikun wang Honglin Li Song Li wu zhong Xuan Li Xiao Li Pei Hao Key Laboratory of Synthetic biology CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China Changchun Veterinary Research institute Chinese Academy of Agricultural SciencesChangchun 130122China Key Laboratory of Molecular Virology and Immunology Institut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijing 100850China Academicians Workstation of Jilin Province Changchun University of Chinese MedicineChangchun 130117China East china University of Science and Technology Shanghai 200237China Lingang Laboratory Shanghai 200031China University of chinese academy of sciences Beijing 100049China

Monkeypox was declared a global health emergency by the World Health Organization,and as of March 2023,86,000 confirmed cases and 111 deaths across 110 countries have been *** causal agent,monkeypox virus(MPV)belongs to a large family of double-stranded DNA viruses,Orthopoxviridae,that also includes vaccinia virus(VACV)and *** produces two distinct forms of viral particles during its replication cycles:the enveloped viron(EV)that is released via exocytosis,and the mature viron(MV)that is discharged through lysis of host *** study was designed to develop multi-valent m RNA vaccines against monkeypox EV and MV surface proteins,and examine their efficacy and mechanism of *** m RNA vaccines were produced with different combinations of surface proteins from EV(A35R and B6R),MV(A29L,E8L,H3L and M1R),or EV and MV,and were administered in Balb/c mice to assess their immunogenicity potentials.A dynamic immune response was observed as soon as seven days after initial immunization,while a strong Ig G response to all immunogens was detected with ELISA after two *** higher number of immunogens contributed to a more robust total Ig G response and correlating neutralizing activity against VACV,indicating the additive potential of each immunogen in generating immune response and nullifying VACV ***,the m RNA vaccines elicited an antigen-specific CD4^(+)T cell response that is biased towards *** m RNA vaccines with different combinations of EVand MV surface antigens protected a mouse model from a lethal dose VACV challenge,with the EV and MV antigens-combined vaccine offering the strongest *** findings provide insight into the protective mechanism of multi-valent m RNAvaccines against MPV,and also the foundation for further development of effective and safe m RNA vaccines for enhanced protection against monkeypox virus outbreak.

关键词： monkeypox virus enveloped and mature viron multi-valent mRNA vaccines immune response neutralizing antibody

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Computational neuroscience:a frontier of the 21st century

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National Science Review 2020年第9期7卷 1418-1422页

作者： Xiao-Jing wang Hailan Hu chengcheng Huang Henry Kennedy chengyu Tony Li Nikos Logothetis zhong-Lin Lu Qingming Luo Mu-ming Poo Doris Tsao Si wu Zhaohui wu Xu Zhang Douglas Zhou Center for Neural Science New York University Center for Neuroscience Key Laboratory of Medical Neurobiology of the Ministry of Health of China School of Medicine Zhejiang University Department of Neuroscience and Department of Mathematics Center for the Neural Basis of Cognition University of Pittsburgh Université Claude Bernard Lyon 1 Inserm Stem Cell and Brain Research Institute U1208 institute of Neuroscience State Key Laboratory of Neuroscience Chinese Academy of SciencesCAS Center for Excellence in Brain Science and Intelligence Technology shanghai Center for Brain Science and Brain-Inspired Technology Division of Arts and sciences and NYU-ECNU Institute of Cognitive Neuroscience NYU Shanghai School of Biomedical Engineering Hainan University Huazhong University of Science and Technology-Suzhou institute for Brainsmatics Division of biology and biological Engineering California Institute of Technology Howard Hughes Medical institute School of Electronics Engineering and Computer Science IDG/Mc Govern Institute for Brain Research PKU-Tsinghua Center for Life SciencesPeking University College of Computer Science and Technology Zhejiang University institute of Brain-Intelligence Science and Technology Zhangjiang Lab School of Mathematical sciences MOE-LSCand Institute of Natural Sciences Shanghai Jiao Tong University

THEORY IN NEUROSCIENCE The human brain is a biological organ,weighing about three pounds or 1.4 kg,that determines our behaviors, thoughts,emotions and consciousness. Although comprising only 2%of the total body weigh... 详细信息

关键词： NETWORKS

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scDPN for High-throughput Single-cell CNV Detection to Uncover Clonal Evolution During HCC Recurrence

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Genomics, Proteomics & Bioinformatics 2021年第3期19卷 346-357页

作者： Liang wu Miaomiao Jiang Yuzhou wang Biaofeng Zhou Yunfan Sun Kaiqian Zhou Jiarui Xie Yu zhong Zhikun Zhao Michael Dean Yong Hou Shiping Liu BGI Education Center University of Chinese Academy of SciencesShenzhen 518083China BGI-Shenzhen Beishan Industrial ZoneShenzhen 518083China Shenzhen Key Laboratory of Single-cell Omics BGI-ShenzhenShenzhen 518100China Department of Liver Surgery&Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityMOE Key Laboratory of Carcinogenesis and Cancer InvasionShanghai 200032China School of biology and biological Engineering South China University of TechnologyGuangzhou 510640China Laboratory of Translational Genomics Division of Cancer Epidemiology&GeneticsNational Cancer InstituteGaithersburgMD 20877USA

Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer ***,classical DNA amplification-based methods have low throughput and introduce coverage bias during sample *** developed a single-cell DNA library preparation method without preamplification in nanolitre scale(scDPN)to address these *** method achieved a throughput of up to 1800 cells per run for copy number variation(CNV)***,our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification(MDA)method and showed high sensitivity and accuracy for cell line and tumor tissue *** used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepatocellular carcinoma(HCC).We identified three clonal subpopulations with a multitude of aneuploid alterations across the ***,we observed that a minor clone of the primary tumor containing additional alterations in chromosomes 1q,10q,and 14q developed into the dominant clone in the recurrent tumor,indicating clonal selection during recurrence in ***,this approach provides a comprehensive and scalable solution to understand genome heterogeneity and evolution.

关键词： Single-cell sequencing Hepatocellular carcinoma Heterogeneity Clonal evolution Relapse

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Questions about NgAgo

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Protein & cell 2016年第12期7卷 913-915页

作者： Shawn Burgess Linzhao cheng Feng Gu Zhiwei Huang Shuo Lin Jinsong Li Wei Li Wei Qin Yujie Sun Zhou Songyang Wensheng Wei Qiang wu Haoyi wang Xiaoqun wang Jing-Wei Xiong Jianzhong Xi Hui Yang Bin Zhou Bo Zhang Junjiu Huang National Human Genome Research institute NIH Bethesda MD 20892 USA Division of Hematology in Department of Medicine Johns HopkinsUniversity School of Medicine Baltimore MD 21205 USA Stem cell Program in the institute for cell Engineering Johns Hopkins University School of Medicine Baltimore MD 21205 USA Center for Vision Research Eye Hospital Wenzhou Medical University Wenzhou 325035 China Stem cell and Functional Genomics Laboratory School of LifeSciences Sun Yat-sen University Guangzhou 510275 China HIT Center of Life sciences Harbin Institute of Technology Harbin 150080 China Department of Molecular Cell and Developmental Biology University of California Los Angeles Los Angeles CA 90095 USA institute of biochemistry and cell biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China State Key Laboratory of Stem cell and Reproductive biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China College of Chemical biology and Biotechnology Peking Univer- sity Shenzhen Graduate School Shenzhen 518055 China PKU BIOPIC Beijing 100871 China BIOPIC ICG CLS and School of Life Sciences Peking Univer-sity Beijing 100871 China Center for Comparative Biomedicine Institute of SystemsBiomedicine Shanghai Jiao Tong University Shanghai 200240China institute of Biophysics Chinese Academy of Sciences Beijing100101 China institute of Molecular Medicine Peking University Beijing100871 China College of Engineering Peking University Beiiing 100871 China Laboratory of Disease Models in Non-Human Primates Instituteof Neuroscience Shanghai Chinese Academy of SciencesShanghai 200031 China College of Life sciences Peking University Beijing 100871 China

Dear Editor： Gao et al. published data in Nature Biotechnology （Nat Biotechnol. 2016 May 2） showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute （NgAgo） protein targeted 47 mammalian genomic loci with a 100% success rate and an efficiency of 21.3%-41.3% at various targets. This report led us to test NgAgo＇s utility in various cells and organisms such as mouse and zebrafish for gene editing.

关键词： Supplementary Information Genomic Locus Genome Editing Gene Editing Online Forum

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Perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors

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Cancer Communications 2023年第6期43卷 637-660页

作者： Kayoko Hosaka Chenchen wang Shiyue Zhang Xue Lv Takahiro Seki Yin Zhang Xu Jing Jieyu wu Qiqiao Du Xingkang He Yulong Fan Xuan Li Makoto Kondo Masahito Yoshihara Hong Qian Lihong Shi Ping Zhu Yuanfu Xu Yunlong Yang Tao cheng Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinP.R.China Tianjin institutes of Health Science TianjinP.R.China School of Pharmacology Binzhou Medical UniversityYantaiShandongP.R.China Department of Clinical Laboratory the Second Hospital of Shandong UniversityJinanShandongP.R.China Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University Medical SchoolHangzhouZhejiangP.R.China Center for Hematology and Regenerative Medicine Department of MedicineKarolinska InstituteKarolinska University HospitalStockholmSweden Department of Biosciences and Nutrition Karolinska InstituteHuddingeSweden Department of cellular and Genetic Medicine School of Basic Medical SciencesFudan UniversityShanghaiP.R.China

Background:Tumors possess incessant growth features,and expansion of their masses demands sufficient oxygen supply by red blood cells(RBCs).In adult mammals,the bone marrow(BM)is the main organ regulating hematopoiesis with dedicated *** than BM,extramedullary hematopoiesis is discovered in various pathophysiological ***,whether tumors can contribute to hematopoiesis is completely *** evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other ***,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate ***:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived *** tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in ***-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological *** production of erythroid differentiationspecific cytokine,erythropoietin(EPO),in TME was checked using quantitative polymerase chain reaction(qPCR),enzyme-linked immunosorbent assay(ELISA,magnetic-activated cell sorting and *** investigate BM function in tumor erythropoiesis,BM transplantation mouse models were ***:Genome-wide expression profiling showed that in response to plateletderived growth factor subunit B(PDGF-B),neural/glial antigen 2(NG2)+perivascular localized cells exhibited hematopoietic stem and progenitor-like features and underwent differentiation towards the erythroid ***-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates *** analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived sub

关键词： cancer hematopoiesis PDGF-B perivascular localized cell stem cell tumor vasculature

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The landscape of aging

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Science china(Life sciences) 2022年第12期65卷 2354-2454页

作者： Yusheng Cai Wei Song Jiaming Li Ying Jing Chuqian Liang Liyuan Zhang Xia Zhang Wenhui Zhang Beibei Liu Yongpan An Jingyi Li Baixue Tang Siyu Pei Xueying wu Yuxuan Liu cheng-Le Zhuang Yilin Ying Xuefeng Dou Yu Chen Fu-Hui Xiao Dingfeng Li Ruici Yang Ya Zhao Yang wang Lihui wang Yujing Li Shuai Ma Si wang Xiaoyuan Song Jie Ren Liang Zhang Jun wang Weiqi Zhang Zhengwei Xie Jing Qu Jianwei wang Yichuan Xiao Ye Tian Gelin wang Ping Hu Jing Ye Yu Sun Zhiyong Mao Qing-Peng Kong Qiang Liu Weiguo Zou Xiao-Li Tian Zhi-Xiong Xiao Yong Liu Jun-Ping Liu Moshi Song Jing-Dong J.Han Guang-Hui Liu State Key Laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for Stem cell and Regenerative Medicine Beijing 100101China Frontier Science Center for Immunology and Metabolism Medical Research InstituteCollege of Life SciencesWuhan UniversityWuhan 430071China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of chinese academy of sciences Beijing 100049China State Key Laboratory of Stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Peking University International Cancer institute Peking University Health Science CenterPeking UniversityBeijing 100191China School of Pharmaceutical sciences Tsinghua UniversityBeijing 100084China State Key Laboratory of Molecular Developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China School of Pharmaceutical sciences Beijing Advanced Innovation Center for Structural BiologyMinistry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologyTsinghua UniversityBeijing 100084China Colorectal Cancer Center/Department of Gastrointestinal Surgery Shanghai Tenth People’s Hospital Affiliated to Tongji UniversityShanghai 200072China Department of Geriatrics Medical Center on Aging of Shanghai Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China International Laboratory in Hematology and Cancer Shanghai Jiaotong University School of Med

Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to *** is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and ***,the growing emphasis on “healthy aging” raises a series of important questions in life and social *** recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological *** an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.

关键词： aging mechanism intervention

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Impact factors of Blastocystis hominis infection in persons living with human immunodeficiency virus:a large-scale,multi-center observational study from china

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Infectious Diseases of Poverty 2023年第5期12卷 95-96页

作者： Shun-Xian Zhang Ji-Chun wang zhong-Wei Li Jin-Xin Zheng Wen-Ting Zhou Guo-Bing Yang Ying-Fang Yu Xiu-Ping wu Shan Lv Qin Liu Mu-Xin Chen Yan Lu Zhi-Hui Dou Da-Wei Zhang Wen-Wen Lv Lei wang Zhen-Hui Lu Ming Yang Pei-Yong Zheng Yue-Lai Chen Li-Guang Tian Xiao-Nong Zhou Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai China chinese Center for Disease Control and Prevention (chinese Center for Tropical Diseases Research) NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research On Tropical Diseases National Institute of Parasitic Diseases Shanghai China School of Global Health Chinese Center for Tropical Diseases Research-Shanghai Jiao Tong University School of Medicine Shanghai China Department of Science and Technology Chinese Center for Disease Control and Prevention Beijing China Gansu Province People’s Hospital Gansu Provincial Hospital Lanzhou China National Health Commission (NHC) Key Laboratory of Biosafety National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing China Gansu Provincial Center for Disease Control and Prevention Lanzhou China National Center for AIDS/STD Control and Prevention China Center for Disease Control and Prevention Beijing China The People’s Liberation Army 302 Hospital Beijing China Clinical Research institute Shanghai Jiao Tong University School of Medicine Shanghai China

Background Blastocystis hominis(Bh)is zoonotic parasitic pathogen with a high prevalent globally,causing opportunistic infections and diarrhea *** immunodeficiency virus(HIV)infection disrupts the immune system by depleting CD4^(+)T lymphocyte(CD4^(+)T)cell counts,thereby increasing Bh infection risk among persons living with HIV(PLWH).However,the precise association between Bh infection risk and HIV-related biological markers and treatment processes remains poorly ***,the purpose of the study was to explore the association between Bh infection risk and CD4^(+)T cell counts,HIV viral load(VL),and duration of interruption in antiviral therapy among *** A large-scale multi-center cross-sectional study was conducted in china from June 2020 to December *** genetic presence of Bh in fecal samples was detected by real-time fluorescence quantitative polymerase chain reaction,the CD4^(+)T cell counts in venous blood was measured using flowcytometry,and the HIV VL in serum was quantified using fluorescence-based *** cubic spline(RCS)was applied to assess the non-linear association between Bh infection risk and CD4^(+)T cell counts,HIV VL,and duration of interruption in highly active antiretroviral therapy(HARRT).Results A total of 1245 PLWH were enrolled in the study,the average age of PLWH was 43 years[interquartile range(IQR):33,52],with 452(36.3%)being female,50.4%(n=628)had no immunosuppression(CD4^(+)T cell counts>500 cells/μl),and 78.1%(n=972)achieved full virological suppression(HIV VLcell counts(Pfor nonlinearity<0.001,L-shaped),HIV VL(Pfor nonlinearity<0.001,inverted U-shaped),and duration of interruption in HARRT(Pfor nonlinearity<0.001,inverted U-shaped).Conclusions

关键词： Blastocystis hominis Human immunodeficiency virus Viral load Non-linear association Restricted cubic spline Propensity score china

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Somatosensory Neuron Types Identified by High-Coverage Single-cell RNA-Sequencing and Functional Heterogeneity

Somatosensory Neuron Types Identified by High-Coverage Singl...

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长三角地区神经科学论坛2016暨第八次会员代表大会

作者：李昌林 Kai-cheng Li Dan wu Yan Chen Hao Luo Jing-Rong Zhao Sa-Shuang wang Ming-Ming Sun Ying-Jin Lu Yan-Qing zhong Xu-Ye Hu Rui Hou Bei-Bei Zhou Lan Bao Hua-Sheng Xiao Xu Zhang institute of Neuroscience and State Key Laboratory of Neuroscience CAS Center for Excellence in Brain Science Shanghai Institutes for Biological Sciences Chinese Academy of Sciences School of Life Science and Technology Shanghai Tec University National Engineering Center for Biochip at shanghai shanghai Clinical Center Chinese Academy of Sciences/Xu Hui Central Hospital State Key Laboratory of cell biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences

Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron-typing with the sensory phenotypes. Here, we classified somatosensory neurons of the mouse dorsal root ganglion（DRG） by highcoverage single-cell RNA-sequencing（10,950 ± 1,218 genes per neuron） and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli were recorded using an in vivo whole-cell patch-clamp technique and classified by neuron-type genetic markers. Small-diameter DRG neurons were classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptor（MHN）. Each of the MHN types was further sorted into two subtypes. Large DRG neurons were categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors（MNs） marked by BAI1-associated protein 2-like 1（Baiap2l1） expression. Mechanoreceptors marked by trafficking protein particle complex 3-like and Baiap2/1-marked MNs were further clustered into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases.

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基于加权基因共表达网络分析识别抑郁症的差异表达基因模块

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上海交通大学学报（医学版） 2021年第6期41卷 724-731页

作者：耿瑞杰姚琳黄欣欣禹顺英苑成梅洪武吕钦谕王庆中易正辉方贻儒复旦大学附属中山医院心理医学科上海200032 上海交通大学医学院附属精神卫生中心精神科上海200030 上海市浦东新区南汇精神卫生中心精神科上海201399 上海中医药大学中药研究所神经药理实验室上海201203 中国科学院脑科学与智能技术卓越创新中心上海200031 上海市重性精神病重点实验室上海201108

目的·采用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)探索抑郁症相关的差异基因模块及其枢纽基因,并对差异基因模块进行生物功能注释。方法·在之前对8例抑郁症患者及8名健康对照者(对照组)的外周血... 详细信息

目的·采用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)探索抑郁症相关的差异基因模块及其枢纽基因,并对差异基因模块进行生物功能注释。方法·在之前对8例抑郁症患者及8名健康对照者(对照组)的外周血mRNA微阵列分析实验的基础上,应用t检验筛选抑郁症患者与对照组的差异表达基因,通过R软件WGCNA包进行分析;当关联系数阈值设定为0.9时,参数β=14,以此构建基因数据集的共表达网络。应用混合动态树切割方法切割网络产生基因模块。采用Pearson相关性检验评估基因模块和抑郁症之间的相关性,分别选取与抑郁症正相关性和负相关性最强的基因模块,并选择模块内连接性最强的前3个基因作为枢纽基因。最后利用GO功能富集分析和KEGG通路分析对2个模块进行功能注释。结果·从16个样品中获得4125个差异表达基因,从中识别出9个基因模块,选择蓝色(blue)模块(R=-0.91,P=0.000)和青色(cyan)模块(R=0.76,P=0.000)进行后续研究。Blue模块的枢纽基因为JAM2(junctional adhesion molecule 2)、SCRN2(secernin 2)和IGHV7-81(immunoglobulin heavy variable 7-81);cyan模块的枢纽基因为SCFD2(Sec1 family domain containing 2)、NR5A2(nuclear receptor subfamily 5 group A member 2)和KCNMA1(potassium calcium-activated channel subfamily M alpha 1)。生物功能注释发现,cyan模块的基因主要富集在胚胎发育、细胞生长、免疫及炎症等生物学过程,blue模块基因则主要在物质加工转运及感染等方面富集。结论·得到2个外周血mRNA基因模块和6个枢纽基因(JAM2、SCRN2、IGHV7-81、SCFD2、NR5A2和KCNMA1),可能与抑郁症显著相关;这2个基因模块可能在胚胎发育、免疫和炎症反应、物质加工转运等方面发挥作用。

关键词：抑郁症加权基因共表达网络分析差异表达基因枢纽基因

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