Fig. 8: Emp1 overexpression or CERS2 inhibition protects HSCs against IR-induced injury.

A Experimental schematic. HSCs from wild-type C57BL/6J mice were infected with retrovirus to force Emp1 overexpression, followed by a dose of 2 Gy γ-irradiation. Two hours after radiation exposure, a competitive transplantation assay was conducted in which IR-treated HSCs were used. B The percentages of donor-derived cells in PB at indicated times (n = 5 recipients per group). C The percentages of donor-derived myeloid cells, B cells, and T cells in PB cells of recipient mice at 4 months after transplantation (n = 5 recipients per group). D The percentages of donor-derived BM cells, LK, LSK, and HSCs in BM of recipients at 4 months after transplantation (n = 5 recipients per group). E Experimental scheme. HSCs from wild-type C57BL/6J mice were treated with DMSO or fumonisin B1 (10 μM) for 24 h, followed by a dose of 2 Gy γ-irradiation. Two hours after radiation exposure, a competitive transplantation assay was conducted in which IR-treated HSCs were used. Additionally, another group of HSCs was cultured for 24 h post-irradiation, followed by flow cytometry analysis. F Flow cytometry analysis of protein aggregate levels in HSCs (CD48⁻CD150⁺LSK) using ProteoStat staining. Right graph represents the MFI of ProteoStat in HSCs (n = 5 mice per group). G Graphs represent the MFI of p-IRE1 (left) and p-PERK (right) in HSCs (CD48⁻CD150⁺LSK) using flow cytometry staining and analysis (n = 5 mice per group). H The percentages of donor-derived cells in PB at indicated times (n = 5 recipients per group). I The percentages of donor-derived myeloid cells, B cells, and T cells in PB cells of recipient mice at 4 months after transplantation (n = 5 recipients per group). J The percentages of donor-derived BM cells, LK, LSK, and HSCs in BM of recipients at 4 months after transplantation (n = 5 recipients per group). K A proposed model scheme represents the roles and molecular mechanisms of EMP1 safeguarding HSCs via CERS2-mediated sphingolipid metabolism. All statistical analyses were performed using two-tailed unpaired Student’s t-test. Data are shown as mean ± SD. Results are representative of two independent experiments. Source data are provided as a Source Data file.