Trans-omics Impact of Thymoproteasome in Cortical Thymic Epithelial Cells
Izumi Ohigashi,
Yu Tanaka,
Kenta Kondo,
Sayumi Fujimori,
Hiroyuki Kondo,
Amy C. Palin,
Victoria Hoffmann,
Mina Kozai,
Yosuke Matsushita,
Shinsuke Uda,
Ryo Motosugi,
Jun Hamazaki,
Hiroyuki Kubota,
Shigeo Murata,
Keiji Tanaka,
Toyomasa Katagiri,
Hidetaka Kosako,
Yousuke Takahama
Affiliations
Izumi Ohigashi
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan
Yu Tanaka
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Kenta Kondo
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Sayumi Fujimori
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan
Hiroyuki Kondo
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan
Amy C. Palin
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Victoria Hoffmann
Division of Veterinary Resources, Office of Research Services, NIH, Bethesda, MD 20892, USA
Mina Kozai
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan
Yosuke Matsushita
Division of Genome Medicine, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan
Shinsuke Uda
Division of Integrated Omics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
Ryo Motosugi
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan
Jun Hamazaki
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan
Hiroyuki Kubota
Division of Integrated Omics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
Shigeo Murata
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan
Keiji Tanaka
Tokyo Metropolitan Institute for Medical Science, Tokyo 156-8506, Japan
Toyomasa Katagiri
Division of Genome Medicine, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan
Hidetaka Kosako
Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan
Yousuke Takahama
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Corresponding author
Summary: The thymic function to produce self-protective and self-tolerant T cells is chiefly mediated by cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs). Recent studies including single-cell transcriptomic analyses have highlighted a rich diversity in functional mTEC subpopulations. Because of their limited cellularity, however, the biochemical characterization of TECs, including the proteomic profiling of cTECs and mTECs, has remained unestablished. Utilizing genetically modified mice that carry enlarged but functional thymuses, here we show a combination of proteomic and transcriptomic profiles for cTECs and mTECs, which identified signature molecules that characterize a developmental and functional contrast between cTECs and mTECs. Our results reveal a highly specific impact of the thymoproteasome on proteasome subunit composition in cTECs and provide an integrated trans-omics platform for further exploration of thymus biology. : Ohigashi et al. show that the use of cyclin D1-transgenic mice allows quantitative proteomic analysis of cortical and medullary thymic epithelial cells (TECs). Results provide a trans-omics platform for further exploration of TEC biology and reveal the specific impact of the thymoproteasome on proteasome subunit composition in cortical TECs. Keywords: cortical thymic epithelial cells, medullary thymic epithelial cells, proteome, trans-omics, thymoproteasome, Psmb11, cyclin D1
