Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-11-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221367111500274X |
| _version_ | 1811320071040008192 |
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| author | Tomokatsu Ikawa Kyoko Masuda Mirelle J.A.J. Huijskens Rumi Satoh Kiyokazu Kakugawa Yasutoshi Agata Tomohiro Miyai Wilfred T.V. Germeraad Yoshimoto Katsura Hiroshi Kawamoto |
| author_facet | Tomokatsu Ikawa Kyoko Masuda Mirelle J.A.J. Huijskens Rumi Satoh Kiyokazu Kakugawa Yasutoshi Agata Tomohiro Miyai Wilfred T.V. Germeraad Yoshimoto Katsura Hiroshi Kawamoto |
| author_sort | Tomokatsu Ikawa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T12:53:54Z |
| format | Article |
| id | doaj.art-75165807deb44108b1dc967407f67658 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-13T12:53:54Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-75165807deb44108b1dc967407f676582022-12-22T02:46:07ZengElsevierStem Cell Reports2213-67112015-11-015571672710.1016/j.stemcr.2015.09.012Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem CellsTomokatsu Ikawa0Kyoko Masuda1Mirelle J.A.J. Huijskens2Rumi Satoh3Kiyokazu Kakugawa4Yasutoshi Agata5Tomohiro Miyai6Wilfred T.V. Germeraad7Yoshimoto Katsura8Hiroshi Kawamoto9Laboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, JapanLaboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, JapanDivision of Haematology, Department of Internal Medicine, Maastricht University Medical Centre, PO Box 616, 6220 MD Maastricht, the NetherlandsLaboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, JapanLaboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, JapanDepartment of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, JapanLaboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, JapanDivision of Haematology, Department of Internal Medicine, Maastricht University Medical Centre, PO Box 616, 6220 MD Maastricht, the NetherlandsLaboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, JapanLaboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, JapanSelf-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.http://www.sciencedirect.com/science/article/pii/S221367111500274X |
| spellingShingle | Tomokatsu Ikawa Kyoko Masuda Mirelle J.A.J. Huijskens Rumi Satoh Kiyokazu Kakugawa Yasutoshi Agata Tomohiro Miyai Wilfred T.V. Germeraad Yoshimoto Katsura Hiroshi Kawamoto Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells Stem Cell Reports |
| title | Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells |
| title_full | Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells |
| title_fullStr | Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells |
| title_full_unstemmed | Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells |
| title_short | Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells |
| title_sort | induced developmental arrest of early hematopoietic progenitors leads to the generation of leukocyte stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S221367111500274X |
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