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M. Hu et al.
7H), thereby significantly alleviating irradiation-induced damage (Figure 7J; Online Supplementary Figure S7C). These effects were abrogated by a specific NF-κB inhibitor, QNZ38 (Figure 7J; Online Supplementary Figure S7C). In conclusion, our findings demonstrate that miR- 21 can also protect HSC from radiation damage.
Discussion
The maintenance of HSC homeostasis contributes to the continuous supplementation of blood cells throughout the lifetime.1,6 In the past few decades, studies aimed at researching hematopoiesis have revealed many factors
ABC
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Figure 4. miR-21 deficiency intrinsically compromises hematopoietic stem cell function in long-term reconstitution. (A-C) CD45.2+ miR-21fl/fl or miR-21∆/∆ bone mar- row (BM) cells were transplanted into 10.0 Gy-irradiated CD45.1+ recipients. Sixteen weeks later, BM cells harvested from primary recipients were transplanted into 10.0 Gy-irradiated secondary CD45.1+ recipients. The survival rates of these recipient mice after primary (B) and secondary (C) non-competitive bone marrow trans- plantation (BMT) were monitored (n=10 mice per group). (D-H) CD45.2+ miR-21fl/fl or miR-21∆/∆ BM cells, mixed (1:1) with CD45.1+ competitor BM cells, were trans- planted into 10.0 Gy-irradiated CD45.1+ recipients. Sixteen weeks later, BM cells harvested from primary recipients were transplanted into 10.0 Gy-irradiated sec- ondary CD45.1+ recipients. At the indicated times, CD45.2+ donor chimerism and lineage distribution in recipients’ peripheral blood (PB) after primary (E, F) and sec- ondary (G, H) competitive BMT were analyzed by flow cytometry (n=8 mice per group). The data shown on lineage distribution were obtained at 16 weeks after primary and secondary competitive BMT. (I-K) CD45.2+ BM cells from miR-21fl/fl;Mx1-Cre- or miR-21fl/fl;Mx1-Cre+ mice without pIpC treatment, together (1:1) with CD45.1+ com- petitor BM cells, were transplanted into 10 Gy-irradiated CD45.1+ WT recipients. Eight weeks after transplantation, miR-21 deletion was induced by injecting the recipients with pIpC. At the indicated times, the donor chimerism (J) and lineage distribution (K) in recipients’ PB after transplantation were analyzed by flow cytom- etry. The data shown on lineage distribution were obtained at 24 weeks after transplantation. A diagram is shown in the left panel. All data are shown as means ± standard deviation. *P<0.05, **P<0.01.
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haematologica | 2021; 106(2)