CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells
In the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identif...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-06-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368916X694201 |
| _version_ | 1818342342221889536 |
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| author | Yoshikazu Matsuoka Masaya Takahashi Keisuke Sumide Hiroshi Kawamura Ryusuke Nakatsuka Tatsuya Fujioka Yoshiaki Sonoda M.D., Ph.D. |
| author_facet | Yoshikazu Matsuoka Masaya Takahashi Keisuke Sumide Hiroshi Kawamura Ryusuke Nakatsuka Tatsuya Fujioka Yoshiaki Sonoda M.D., Ph.D. |
| author_sort | Yoshikazu Matsuoka |
| collection | DOAJ |
| description | In the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identified very primitive human cord blood (CB)-derived CD34 – severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection method. In this study, we investigated the roles of the MPL expression in the human primitive HSC compartment. The SRC activities of the highly purified CB-derived 18Lin – CD34 +/– MPL +/– cells were analyzed using NOG mice. In the primary recipient mice, nearly all mice that received CD34 +/– MPL +/– cells were repopulated with human CD45 + cells. Nearly all of these mice that received CD34 + MPL +/– and CD34 – MPL – cells showed a secondary repopulation. Interestingly, the secondary recipient mice that received CD34 +/– MPL – cells showed a distinct tertiary repopulation. These results clearly indicate that the CD34 +/– SRCs not expressing MPL sustain a long-term (LT) (>1 year) human cell repopulation in NOG mice. Moreover, CD34 – SRCs generate CD34 + CD38 – CD90 + SRCs in vitro and in vivo. These findings provide a new concept that CD34 – MPL – SRCs reside at the apex of the human HSC hierarchy. |
| first_indexed | 2024-12-13T16:13:10Z |
| format | Article |
| id | doaj.art-af009ca6a1694058b05ca1c4d3a0a2c5 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-13T16:13:10Z |
| publishDate | 2017-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-af009ca6a1694058b05ca1c4d3a0a2c52022-12-21T23:38:53ZengSAGE PublishingCell Transplantation0963-68971555-38922017-06-012610.3727/096368916X694201CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem CellsYoshikazu Matsuoka0Masaya Takahashi1Keisuke Sumide2Hiroshi Kawamura3Ryusuke Nakatsuka4Tatsuya Fujioka5Yoshiaki Sonoda M.D., Ph.D.6Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Osaka, JapanDepartment of Pediatrics, Kansai Medical University, Osaka, JapanDepartment of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Osaka, JapanDepartment of Orthopedic Surgery, Kansai Medical University, Osaka, JapanDepartment of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Osaka, JapanDepartment of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Osaka, JapanDepartment of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Osaka, JapanIn the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identified very primitive human cord blood (CB)-derived CD34 – severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection method. In this study, we investigated the roles of the MPL expression in the human primitive HSC compartment. The SRC activities of the highly purified CB-derived 18Lin – CD34 +/– MPL +/– cells were analyzed using NOG mice. In the primary recipient mice, nearly all mice that received CD34 +/– MPL +/– cells were repopulated with human CD45 + cells. Nearly all of these mice that received CD34 + MPL +/– and CD34 – MPL – cells showed a secondary repopulation. Interestingly, the secondary recipient mice that received CD34 +/– MPL – cells showed a distinct tertiary repopulation. These results clearly indicate that the CD34 +/– SRCs not expressing MPL sustain a long-term (LT) (>1 year) human cell repopulation in NOG mice. Moreover, CD34 – SRCs generate CD34 + CD38 – CD90 + SRCs in vitro and in vivo. These findings provide a new concept that CD34 – MPL – SRCs reside at the apex of the human HSC hierarchy.https://doi.org/10.3727/096368916X694201 |
| spellingShingle | Yoshikazu Matsuoka Masaya Takahashi Keisuke Sumide Hiroshi Kawamura Ryusuke Nakatsuka Tatsuya Fujioka Yoshiaki Sonoda M.D., Ph.D. CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells Cell Transplantation |
| title | CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells |
| title_full | CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells |
| title_fullStr | CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells |
| title_full_unstemmed | CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells |
| title_short | CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells |
| title_sort | cd34 antigen and the mpl receptor expression defines a novel class of human cord blood derived primitive hematopoietic stem cells |
| url | https://doi.org/10.3727/096368916X694201 |
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