egnScmanyDeuceoMeuceoMegnSgncneuqeSgngamI li iill llil iOur lab aims to determine epigenomic and transcriptomic changes in a 16Mark 1Mark 2Mark 3Epigenome Technology DevelopmentMouse Ageing AtlasSingle nucleosome imaging & sequencingSPF/GFSingle cell ATAC & RNA-seqcomprehensive manner in various models by either developing our own technology or applying the most advanced available technologies, such as sin-gle-cell genomics. Such information will be utilized to gain insights into various biological questions at the molecular level. Our current major focus is ageing, which is thought to underlie the pathogenesis of many diseases.Enabling genomic mapping of multiple histone modifications at single-nucleosome resolutionTo increase epigenomic resolution, we are developing a method to deter-mine multiple targets (histone modifications) at the single-nucleosome level. We first carry out single-molecule imaging using fluorophore-labeled antibod-ies that are specific for different histone marks. Proteins are removed after im-aging of the antibodies, so that the genomic DNA that was wrapped around the nucleosomes is left at the same position in the flowcell and can be sequenced by single molecule sequencing (Figure). By applying such technology to various models, we believe that we will be able to gain better epigenomic insights into various biological questions.Construction of a Mouse Ageing Atlas with single-cell genomicsWe are generating single-cell genomics (scATAC-seq and 5’ scRNA-seq) datasets of various tissues from both SPF and germ-free mice at various ages, as well as lipidomics (in collaboration with the Arita lab, IMS), metabolomics and microbiome (metagenomics, in collaboration with the Ohno lab, IMS). Such a rich collection of multi-omics datasets will likely provide us with an unbiased insight at many different levels, including the effect of the microbiome, into the complex biological phenomena of ageing.Understanding the secrets of plant stem cells by applying single-cell genomics (RNA- and ATAC-seq) to plant tissuesWe are carrying out scRNA-seq on meristem tissues, which are enriched with stem cells, from various plant models in an attempt to gain insights into the mechanism of plant stem cell maintenance, which is thought to be the foun-dation for plant longevity and regenerative ability.Figure: Summary of research activitiesNovel epigenome technology development and applica-tion of single-cell genomics in various models.Recent Major PublicationsHashimoto K, Kouno T, Ikawa T, Hayatsu N, Miyajima Y, Yabukami H, Terooatea T, Sasaki T, Suzuki T, Valentine M, Pascarella G, Okazaki Y, Suzuki H, Shin JW, Minoda A, Taniuchi I, Okano H, Arai Y, Hirose N, Carninci P. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians. Proc Natl Acad Sci U S A 116, 24242-24251 (2019)Watanabe K, Liu Y, Noguchi S, Murray M, Chang JC, Kishima M, Nishimura H, Hashimoto K, Minoda A, Suzuki H. OVOL2 induces mesenchymal-to-epithelial transition in fibroblasts and enhances cell-state reprogramming towards epithelial lineages. Sci Rep 9, 6490 (2019)Invited presentationsMinoda A. “Chromatin state analysis at the single mol-ecule resolution” The Molecular Biology Society of Japan (Japan/Online) December 2020Minoda A. “Single cell analyses of ageing tissues with and without microbiota” 10x Genomics APAC User Group Meeting (Online) November 2020Minoda A. “Two sides of the same ‘COVID-19’ coin” The impact of the COVID- 19 crisis on women in science: Challenges and solutions (Online) September 2020Minoda A. “Providing the way to a successful single cell multi-omics analyses” Dolomite Bio-Illumina Webinar (Online) September 2020Minoda A. “Mouse Ageing Atlas” The 1st International Symposium on Human InformatiX (Kyoto, Japan) Febru-ary 2020Laboratory for Cellular EpigenomicsTeam Leader: Aki Minoda
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