Document Detail


Marginal expression of CXCR4 on c-kit(+)Sca-1 (+)Lineage (-) hematopoietic stem/progenitor cells.
MedLine Citation:
PMID:  19937482     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 are the key regulatory molecules of hematopoietic stem cell (HSC) migration and engraftment to the bone marrow (BM) microenvironment. However, the significance of the ligand-receptor complex on HSC in steady-state BM is not clear. There is currently a lack of information as to how CXCR4 is expressed on HSCs. We herein demonstrate that c-kit(+)Sca-1(+)Lineage(-) (KSL) cells freshly isolated from BM expressed very low to undetectable levels of CXCR4. Two hours of incubation at 37 degrees C quickly up-modulated the receptor expression on KSL cells. Protein synthesis was not required for this early stage up-regulation, thus suggesting the emergence of intracellularly pooled receptors to the cell surface. However, protein synthesis was involved at the later stage of up-regulation. The up-regulated CXCR4 was functional, as evidenced by the fact that the incubated KSL cells more efficiently migrated to the SDF-1 gradient in vitro. Therefore, although KSL cells are able to express functional CXCR4, the receptors are only marginally expressed in the steady-state BM microenvironment. These observations therefore indicate the limited role of the SDF-1-CXCR4 axis on HSC functionality in a static BM environment.
Authors:
Yutaka Sasaki; Yoshikazu Matsuoka; Makoto Hase; Takayuki Toyohara; Mari Murakami; Masaya Takahashi; Ryusuke Nakatsuka; Yasushi Uemura; Yoshiaki Sonoda
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-26
Journal Detail:
Title:  International journal of hematology     Volume:  90     ISSN:  1865-3774     ISO Abbreviation:  Int. J. Hematol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-03-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-60     Citation Subset:  IM    
Affiliation:
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Moriguchi, Osaka, 570-8506, Japan. sasakiy@takii.kmu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Ly
Bone Marrow
Chemokine CXCL12 / physiology
Hematopoietic Stem Cells
Membrane Proteins
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins c-kit
Receptors, CXCR4 / analysis*,  biosynthesis,  physiology
Chemical
Reg. No./Substance:
0/Antigens, Ly; 0/Chemokine CXCL12; 0/Cxcl12 protein, mouse; 0/Ly6a protein, mouse; 0/Membrane Proteins; 0/Receptors, CXCR4; EC 2.7.10.1/Proto-Oncogene Proteins c-kit

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