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Lineage relationship of CD8^＋ T cell subsets is revealed by progressive changes in the epigenetic landscape

Cellular & Molecular Immunology 2016年第4期13卷 502-513页

作者： j.seph G. Crompton Manikandan Narayanan Suresh Cuddapah Rahul Roychoudhuri Yun j. Wenj.ng Yang shashank j. patel Madhusudhanan Sukumar Douglas C. Palmer Weiqun Peng Ena Wang Francesco M. Marincola Christopher A. Klebanoff Kej. Zhao j.hn S. Tsang Luca Gatt-inoni Nicholas P. Restifo Surgery Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA Cambridge Institute for Medical Research University of Cam bridge Cambridge CB20XY UK Systems Genomics and Bioinformatics Unit Laboratory of Systems Biology National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD 20892 USA Department of Environmental Medicine New York University School of Medicine Tuxedo NY 10987 USA Experimental Transplantation and Immunology Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA Department of Physics The George Washington University Washington DC 20052 USA Research Branch Sidra Medical and Research Centre Doha Qatar Infectious Disease and Immunogenetics Section Department of Transfusion Medicine Clinical Center National Institutes of Health Bethesda MD 20892 USA Clinical Investigator Development Program NCI/NIH Bethesda MD 20892 USA Systems Biology Center National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892 USA. Lombardi Comprehensive Cancer Center Georgetown University Washington. DC 20007. United States. Bethesda. MD 20892. USA.

To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed upon T-cell differentiation, we investigated the genomic landscape of histone modifications in naive and memory CD8＋ T cells. Using a ChlP-Seq approach coupled with global gene expression profiling, we generated genome-wide histone H3 lysine 4 （H3K4me3） and H3 lysine 27 （H3K27me3） trimethylation maps in naive, T memory stem cells, central memory cells, and effector memory cells in order to gain insight into how histone architecture is remodeled during T cell differentiation. We show that H3K4me3 histone modifications are associated with activation of genes, while H3K27me3 is negatively correlated with gene expression at canonical loci and enhancers associated with T-cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified T memory stem cells from other CD8＋ T-cell subsets. Taken together, our results suggest that CD8＋ lymphocytes undergo chromatin remodeling in a progressive fashion. These findings have maj.r implications for our understanding of peripheral T-cell ontogeny and the formation of immunological memory.

关键词： TRANSCRIPTION FACTOR STEM-CELLS MEMORY EFFECTOR DIFFERENTIATION BET FATE LYMPHOCYTES MAINTENANCE GENERATION

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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Louj.n Slitin j.kob Neef shashank S.Chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,j.. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona j.lia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of maj.r disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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Nature：死亡的肿瘤细胞释放出胞内钾离子来阻断免疫系统

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现代生物医学进展 2016年第31期16卷 I0002-I0002页

作者： Robert Eil, Suman K. Vodnala, David Clever, Christopher A. Klebanoff, Madhusudhanan Sukumar, j.nny H. Pan, Douglas C. Palmer, Alena Gros, Tori N. Yamamoto, shashank j. patel, Geoffrey C. Guittard, Zhiya Yu, David S. Schrump, W. Marston Linehan, Nicholas P. Restifo Christopher A. Klebanoff Valentina Carbonaro, Klaus Okkenhaug, Rahul Roychoudhuri National Cancer Institute National Institutes of Health (NIH) Bethesda Maryland 20892 USA Center for Cell Engineering and Department of Medicine Memorial Sloan Kettering Cancer Center New York New York 10065 USA Laboratory of Lymphocyte Signalling and Development The Babraham Institute Cambridge CB22 3AT UK

在一项新的研究中。来自美国国家癌症研究所和英国巴布拉汉研究所的研究人员发现当肿瘤组织死亡时从它当中泄露出来的一种无机离子起着阻止抗肿瘤免疫细胞发挥功能的作用。这一发现为开发调动免疫系统抵抗癌症的疗法提供一种新的方法。... 详细信息

在一项新的研究中。来自美国国家癌症研究所和英国巴布拉汉研究所的研究人员发现当肿瘤组织死亡时从它当中泄露出来的一种无机离子起着阻止抗肿瘤免疫细胞发挥功能的作用。这一发现为开发调动免疫系统抵抗癌症的疗法提供一种新的方法。相关研究结果在线发表在Nature期刊上。

关键词：免疫系统肿瘤细胞死亡钾离子免疫细胞无机离子肿瘤组织研究人员

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Investigation on Virtual State Contribution to Gauge Invariant Cross Section of e+e-→j.ψ+ηcin Bethe-Salpeter Framework

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j.urnal of Modern Physics 2014年第11期5卷 1027-1035页

作者： shashank Bhatnagar Ming Li Shiyuan Li Department of Physics Addis Ababa University Addis Ababa Ethiopia School of Physics Shandong University Jinan China

It is shown that the virtual states and relative momentum of the constituents of the bound states are very important for the cross section of the process e+e-→j.ψ+ηc with the help of the Bethe-Salpeter wave function description of the bound states. The gauge invariance of the cross section is demonstrated. The numerical results can explain the experimental data.

关键词： Bethe-Salpeter Wave Function Virtual States Relative Momentum

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单细胞技术揭示肝癌免疫图谱与动态特征

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科学新闻 2020年第2期 41-41页

作者：彭吉润任仙文张泽民刘康 Qiming Zhang Yao He Nan Luo shashank j.patel Yanj.e Han Ranran Gao Madhura Modak Sebastian Carotta Christian Haslinger David Kind Gregory W.Peet Guoj.e Zhong Shuangj.a Lu Weihua Zhu Yilei Mao Mengmeng Xiao Michael Bergmann Xueda Hu Sid P.Kerkar Anne B.Vogt Stefan Pflanz 首都医科大学附属北京世纪坛医院胃肠及肝胆肿瘤外科北京大学生物医学前沿创新中心(BIOPIC) 北京未来基因诊断高精尖创新中心(ICG) 勃林格殷格翰公司

文章简介肝细胞癌是世界范围内死亡率排名第三的癌症,其中中国的肝癌发病率居世界之先。肿瘤存在多种免疫逃逸机制,提出了研究肿瘤微环境中不同免疫细胞状态的重要性。而不同类型的单细胞测序技术则是研究不同类型免疫细胞的状态和动态... 详细信息

文章简介肝细胞癌是世界范围内死亡率排名第三的癌症,其中中国的肝癌发病率居世界之先。肿瘤存在多种免疫逃逸机制,提出了研究肿瘤微环境中不同免疫细胞状态的重要性。而不同类型的单细胞测序技术则是研究不同类型免疫细胞的状态和动态的有力手段。本研究结合了两种单细胞测序技术,充分发挥不同数据类型的优势,获得高分辨率的肝癌免疫图谱。肿瘤中的树突状细胞是重要的抗原呈递细胞,除传统的树突状细胞外,本研究鉴定出一群高表达LAMP3,CCR7等与细胞

关键词：肝癌患者免疫细胞癌旁组织单细胞动态特征

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