title: Induced Developmental Arrest of Early Hematopoietic Progenitors   Leads to   the Generation of Leukocyte Stem Cells.
abstract: Self-renewal potential and multipotency are hallmarks of a stem cell. It is generally accepted that acquisition of such stemness requires rejuvenation of somatic cells through reprogramming of their genetic and epigenetic status.We show here that a simple block of cell differentiation is sufficient to induce and maintain stem cells. By overexpression of the transcriptional inhibitor ID3 in murine hematopoietic progenitor cells and cultivation under B cell induction conditions, the cells undergo developmental arrest and enter a self-renewal cycle. These cells can be maintained in vitro almost indefinitely, and the long-term cultured cells exhibit robust multi-lineage reconstitution when transferred into irradiated mice. These cells can be cloned and re-expanded with 50% plating efficiency, indicating that virtually all cells are self-renewing. Equivalent progenitors were produced from human cord blood stem cells, and these will ultimately be useful as a source of cells for immune cell therapy.
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. Electronic address: tomokatsu.ikawa@riken.jp.
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: Division of Haematology, Department of Internal Medicine, Maastricht University Medical Centre, PO Box 616, 6220 MD Maastricht, the Netherlands.
authors.forename: Mirelle J A J
authors.initials: MJAJ
authors.lastname: Huijskens
authors.affiliation: Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Satoh
authors.affiliation: Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Kakugawa
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 Immune Regeneration, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Miyai
authors.affiliation: Division of Haematology, Department of Internal Medicine, Maastricht University Medical Centre, PO Box 616, 6220 MD Maastricht, the Netherlands.
authors.forename: Wilfred T V
authors.initials: WTV
authors.lastname: Germeraad
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, School of Medicine, Nihon University, Tokyo 173-8610, Japan.
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Katsura
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. Electronic address: kawamoto@frontier.kyoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D019070:Cell Lineage; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D007962:Leukocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL