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The human hematopoietic stem cell compartment is heterogeneous for CXCR4 expression
M Rosu-Myles1, L Gallacher, B Murdoch
1The John P. Robarts Research Institute, Developmental Stem Cell Biology, 100 Perth Drive, London, ON, Canada N6A 5K8, UK.
Summary
Primitive human stem cells expressing stromal derived factor-1alpha receptor (CXCR4) and those without are distinct but possess equal engraftment capacity. CXCR4 expression is not obligatory for stem cell repopulating function.
Area of Science:
- Hematology
- Stem Cell Biology
- Immunology
Background:
- Stromal derived factor-1alpha (SDF-1alpha) is involved in primitive hematopoietic cell chemotaxis.
- This suggests pluripotent stem cells express the SDF-1alpha receptor, CXCR4.
Purpose of the Study:
- To identify and isolate primitive human hematopoietic cell subsets based on CXCR4 expression.
- To investigate the functional differences and in vivo engraftment capacity of CXCR4(+) and CXCR4(-) cells.
Main Methods:
- Flow cytometry and confocal microscopy were used to identify and isolate CXCR4(+) and CXCR4(-) cell subsets.
- In vitro progenitor content and SDF-1alpha response assays were performed.
- Engraftment capacity was assessed by intravenous transplantation into immune-deficient mice.
Main Results:
- CXCR4(+) and CXCR4(-) cells represent discrete primitive blood cell populations with distinct progenitor content and in vitro SDF-1alpha responses.
- Both subsets demonstrated comparable in vivo engraftment capacity.
- Chimeric animals showed the presence of myeloid, lymphoid, and primitive CD34(+) CXCR4(+) cells, regardless of the transplanted subset.
Conclusions:
- The human stem cell compartment is heterogeneous regarding CXCR4 expression.
- CXCR4 expression is not obligatory for stem cell repopulating function, as both CXCR4(+) and CXCR4(-) stem cells exhibit equivalent proliferative and differentiative abilities.