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CD4dull+ hematopoietic progenitor cells in murine bone marrow
M Onishi1, K Nagayoshi, K Kitamura
1Third Department of Internal Medicine, University of Tokyo, Japan.
Insights
Murine bone marrow (BM) contains CD4+ cells, including a rare CD4loGr-1lo subset. These cells possess self-renewal capacity and can differentiate into multiple hematopoietic lineages long-term.
Area of Science:
- Immunology
- Hematopoiesis
- Stem Cell Biology
Background:
- CD4+ cells constitute a small fraction of murine bone marrow (BM).
- Two distinct CD4+ subpopulations exist: mature CD4hiGr-1- and less characterized CD4loGr-1lo cells.
- CD4loGr-1lo cells express B220 and Thy1, but are not enriched for colony-forming units.
Purpose of the Study:
- To investigate the hematopoietic potential and self-renewal capacity of murine CD4loGr-1lo BM cells.
- To determine if CD4loGr-1lo cells can differentiate into multiple hematopoietic lineages.
Main Methods:
- Flow cytometry for CD4, Gr-1, B220, and Thy1 antigen expression analysis.
- Transplantation of CD4loGr-1lo cells into lethally irradiated recipient mice.
- Long-term monitoring of recipient mice for hematopoietic reconstitution and cell differentiation.
Main Results:
- CD4loGr-1lo cells, a rare BM population, were identified.
- Upon transplantation, CD4loGr-1lo cells differentiated into T-cell, B-cell, and myelo-monocyte lineages.
- Donor-derived CD4loGr-1lo cells persisted in recipient BM for at least 16 weeks, indicating self-renewal.
Conclusions:
- Murine CD4loGr-1lo BM cells possess self-renewal capabilities.
- These cells are multipotent and can contribute to long-term hematopoiesis.
- CD4loGr-1lo cells represent a potentially significant stem or progenitor cell population in murine BM.
Abstract:
CD4+ cells comprise approximately 3% to 6% of murine bone marrow (BM) cells. The majority are CD4dull+, but there are two distinct sub populations: CD4 brightly positive Gr-1- cells (CD4hiGr-1-) and CD4+ Gr-1+ cells (CD4loGr-1lo). CD4hiGr-1- cells are considered to be mature T cells by cell surface antigen expression and morphology. CD4loGr-1lo cells, which comprise approximately 0.6% of the BM cells, express small amount of B220 and Thy1 antigens. Interestingly, colony-forming units (CFU)-spleen and CFU-C are not enriched in this population. However, when injected into lethally irradiated mice, CD4loGr-1lo cells were shown to differentiate into T-cell, B-cell, and myelo-monocyte lineages when assayed 26 weeks after transplantation. Furthermore, donor-derived CD4loGr-1lo cells were present in the recipients' BM at least 16 weeks after transplantation. These observations suggest that murine CD4loGr-1lo cells in BM have self-renewal capability and retain the ability to differentiate into at least three lineages in long-term hematopoiesis.