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- W2335180225 abstract "Hematopoietic stem cell (HSC) transplantation is commonly used for treatment of hematopoietic and non-hematopoietic diseases and to investigate HSC function in an experimental setting. Preparation for transplantations often includes myeloablative treatment by total body irradiation (TBI). TBI damages both the host HSCs and their niche, results in high donor cell engraftment levels and is suggested to induce chemokines that attract HSCs to the bone marrow. Studies over the last decade demonstrated that upon transplantation into irradiated recipients, individual murine HSCs differ dramatically in their repopulation potential, myeloid/lymphoid cell output and cycling rate. It is currently unclear whether recipient irradiation contributes to the observed heterogeneity. To address this question, we transplanted different doses of freshly isolated highly purified HSCs into irradiated or untreated mice. As recipients we used C57BL/6W41/W41 mice that bear a c-kit mutation that negatively affects HSC numbers and function. We detected a pronounced delay in reconstitution kinetics of the B cell lineage in non-irradiated mice while the donor chimerism levels in T lymphocytes and short-lived granulocytes developed more quickly. To test how many stem cells engraft in the two transplant scenarios, we utilized a retroviral DNA barcoding method to uniquely label HSCs prior to their transplantation into irradiated or untreated mice and followed barcode contributions in blood for 15 months. The same delay in B-cell reconstitution was observed. However, barcode analysis in peripheral blood demonstrated similar clonal kinetics and heterogeneity of HSC clone sizes, cycling behavior and developmental potential in both irradiated and non-irradiated mice. Upon sacrifice, we were not able to detect differences in the number of contributing HSC clones in the bone marrow, demonstrating that the HSC homing was not affected by irradiation. In summary, our data demonstrate that clonal fluctuations and heterogeneity in the HSC pool are stem cell intrinsic and independent of the effects of irradiation on the niche." @default.
- W2335180225 created "2016-06-24" @default.
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- W2335180225 date "2014-08-01" @default.
- W2335180225 modified "2023-09-25" @default.
- W2335180225 title "Recipient total bone marrow irradiation has no long-term effect on clonal behavior of transplanted murine hematopoietic stem cells" @default.
- W2335180225 doi "https://doi.org/10.1016/j.exphem.2014.07.245" @default.
- W2335180225 hasPublicationYear "2014" @default.
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