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Publication : Acquisition of G₀ state by CD34-positive cord blood cells after bone marrow transplantation.

First Author  Shima H Year  2010
Journal  Exp Hematol Volume  38
Issue  12 Pages  1231-40
PubMed ID  20800645 Mgi Jnum  J:169729
Mgi Id  MGI:4941703 Doi  10.1016/j.exphem.2010.08.004
Citation  Shima H, et al. (2010) Acquisition of G state by CD34-positive cord blood cells after bone marrow transplantation. Exp Hematol 38(12):1231-40
abstractText  OBJECTIVE: Hematopoietic stem cells are kept in a quiescent state in the hypoxic area of the bone marrow, which is essential for hematopoietic stem cell maintenance. However, when and how hematopoietic stem cells acquire their hypoxic state and maintain quiescence has not been fully elucidated. The aim of this study was to understand this process in human hematopoietic stem cells after bone marrow transplantation. MATERIALS AND METHODS: Human CD34-positive cord blood cells were transplanted into nonobese diabetic/severe combined immunodeficient interleukin-2 receptor gamma chain knockout mice. Cell cycle and hypoxia assay analyses were performed, to identify changes in the characteristics of human hematopoietic stem cells following transplantation. Quantitative real-time reverse transcription polymerase chain reaction analysis was used to analyze the transcriptional changes accompanying this transition. RESULTS: Engrafted primitive lineage-negative CD34-positive CD38-negative cells acquired hypoxic state and quiescence in the recipient bone marrow between 4 and 8 weeks, and between 8 and 12 weeks after transplantation, respectively. During 4 and 8 weeks after transplantation, changes in the transcription levels of G regulatory factors, such as CCNC and RBL1, and stem cell regulators, such as Flt3, were also seen, which may be related to the characteristic changes in the cell cycle or oxygenation state. CONCLUSIONS: Behavioral changes of hematopoietic stem cells in their cell cycle and oxygenation state during and after bone marrow engraftment may provide insights into hematopoietic stem cell regulation, mediating the improvement of clinical hematopoietic stem cell transplantation protocols and the eradication of leukemia stem cells.
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