title: Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program.
abstract: In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage. We found that these developmentally arrested T-cell precursors gave rise to functional B cells upon transfer to immunodeficient mice. We further demonstrated that the arrest was almost completely canceled by additional deletion of Pax5 These results indicate that the maintenance of T-cell fate critically requires epigenetic suppression of the B-lineage gene program.
authors.affiliation: Laboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.|Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.|PRESTO (Precursory Research for Embryonic Science and Technology), Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Ikawa
authors.affiliation: Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.|Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Takaho A
authors.initials: TA
authors.lastname: Endo
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Endo
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Isono
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Koseki
authors.affiliation: Laboratory for Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
authors.forename: Rinako
authors.initials: R
authors.lastname: Nakagawa
authors.affiliation: Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kometani
authors.affiliation: Laboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.|Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Takano
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Agata
authors.affiliation: Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.|Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Katsura
authors.affiliation: Laboratory for Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.|Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, 28040 Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vidal
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.|Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008810:Mice, Inbred C57BL; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D063146:Polycomb-Group Proteins; D063150:Polycomb Repressive Complex 1; C489840:Ring1 protein, mouse; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: B cell; T-cell development; epigenetics; lineage commitment; reprogramming; transcription factor