Document Detail

Acquisition of G₀ state by CD34-positive cord blood cells after bone marrow transplantation.
MedLine Citation:
PMID:  20800645     Owner:  NLM     Status:  MEDLINE    
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 γ 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 G₀ 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.
Haruko Shima; Keiyo Takubo; Naoko Tago; Hiroko Iwasaki; Fumio Arai; Takao Takahashi; Toshio Suda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-26
Journal Detail:
Title:  Experimental hematology     Volume:  38     ISSN:  1873-2399     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-01-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1231-40     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
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MeSH Terms
Antigens, CD34 / analysis*
Antigens, CD38 / analysis
Bone Marrow Transplantation*
Fetal Blood / cytology*
G0 Phase*
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells / cytology*
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
fms-Like Tyrosine Kinase 3 / analysis
Reg. No./Substance:
0/Antigens, CD34; 0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; EC protein, human; EC Tyrosine Kinase 3; EC, CD38

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