Marginal expression of CXCR4 on c-kit(+)Sca-1 (+)Lineage (-) hematopoietic stem/progenitor cells.
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.
Sasaki
Yutaka
Y
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan. sasakiy@takii.kmu.ac.jp.
Matsuoka
Yoshikazu
Y
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.
Hase
Makoto
M
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.
Toyohara
Takayuki
T
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.
Murakami
Mari
M
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.|First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Takahashi
Masaya
M
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.|Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Nakatsuka
Ryusuke
R
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.
Uemura
Yasushi
Y
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.
Sonoda
Yoshiaki
Y
Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan.
D000818:Animals; D000950:Antigens, Ly; D001853:Bone Marrow; D054377:Chemokine CXCL12 / Q000502:physiology; D006412:Hematopoietic Stem Cells; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000096:biosynthesis / Q000502:physiology
D000950:Antigens, Ly; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D019009:Proto-Oncogene Proteins c-kit