MeV-scale reheating temperature and cosmological production of light sterile neutrinos

We investigate how sterile neutrinos with a range of masses influence cosmology in MeV-scale reheating temperature scenarios. By computing the production of sterile neutrinos through the combination of mixing and scattering in the early Universe, we find that light sterile neutrinos, with masses and mixings as inferred from short-baseline neutrino oscillation experiments, are consistent with big-bang nucleosynthesis (BBN) and cosmic microwave background (CMB) radiation for the reheating temperature of ${\cal O}(1)$ MeV if the parent particle responsible for reheating decays into electromagnetic components (radiative decay). In contrast, if the parent particle mainly decays into hadrons (hadronic decay), the bound from BBN becomes more stringent. In this case, the existence of the light sterile neutrinos can be cosmologically excluded, depending on the mass and the hadronic branching ratio of the parent particle.Comment: 33 pages, 10 figures, to appear in JCA

Non-Lethal Ionizing Radiation Promotes Aging-Like Phenotypic Changes of Human Hematopoietic Stem and Progenitor Cells in Humanized Mice.

Precise understanding of radiation effects is critical to develop new modalities for the prevention and treatment of radiation-induced damage. We previously reported that non-lethal doses of X-ray irradiation induce DNA damage in human hematopoietic stem and progenitor cells (HSPCs) reconstituted in NOD/Shi-scid IL2rγnull (NOG) immunodeficient mice and severely compromise their repopulating capacity. In this study, we analyzed in detail the functional changes in human HSPCs in NOG mice following non-lethal radiation. We transplanted cord blood CD34+ HSPCs into NOG mice. At 12 weeks post-transplantation, the recipients were irradiated with 0, 0.5, or 1.0 Gy. At 2 weeks post-irradiation, human CD34+ HSPCs recovered from the primary recipient mice were transplanted into secondary recipients. CD34+ HSPCs from irradiated mice showed severely impaired reconstitution capacity in the secondary recipient mice. Of interest, non-lethal radiation compromised contribution of HSPCs to the peripheral blood cells, particularly to CD19+ B lymphocytes, which resulted in myeloid-biased repopulation. Co-culture of limiting numbers of CD34+ HSPCs with stromal cells revealed that the frequency of B cell-producing CD34+ HSPCs at 2 weeks post-irradiation was reduced more than 10-fold. Furthermore, the key B-cell regulator genes such as IL-7R and EBF1 were downregulated in HSPCs upon 0.5 Gy irradiation. Given that compromised repopulating capacity and myeloid-biased differentiation are representative phenotypes of aged HSCs, our findings indicate that non-lethal ionizing radiation is one of the critical external stresses that promote aging of human HSPCs in the bone marrow niche

Repopulation of hematopoiesis by irradiated human HSPCs in secondary recipients.

<p>(A) Changes in chimerism of human hematopoietic cells in the PB of secondary recipients. At 2 weeks post-irradiation, CD34⁺ human HSPCs were purified from the primary recipient mice, and 2 x 10⁶ CD34⁺ HSPCs were transplanted into secondary NOG recipients. Chimerism of CD45⁺ human and mouse hematopoietic cells in the PB are shown in upper panels. The percentages of CD11b⁺ myeloid cells, CD19⁺ B cells, and CD3⁺ T cells in CD45⁺ human hematopoietic cells in the PB are shown in lower panels. PB data of NOG mice just before the irradiation (Pre, n = 27) are also indicated at week 0. Data are presented as mean ± S.D. (0 Gy, n = 5; 0.5 Gy, n = 5; 1.0 Gy, n = 5). (B) Total BM cell numbers and chimerism of CD45⁺ human and mouse hematopoietic cells at 12 weeks after secondary transplantation. (C) Absolute numbers of CD34⁺CD38^- HSCs, CD34⁺CD38⁺ HPCs, CMPs and LMPPs in the BM (bilateral femurs and tibiae) (0 Gy, n = 5; 0.5 Gy, n = 5; 1.0 Gy, n = 5). (D) Numbers of colony-forming cells included in 1,000 CD34⁺ human HSPCs recovered from the BM 12 weeks after secondary transplantation (0–1.0 Gy, n = 3 each). The data in Fig 3B-D are presented as scatter diagrams with median values (bars). <i>P</i>-values for trend were calculated by nonparametric Jonckheere-Terpstra test.</p