Sipa1^−/− niche induces MDS/MPN from normal hematopoietic cells after transplantation following sublethal irradiation. (A) Experimental design, normal hematopoietic cells. Three million normal BM CD45.1⁺ cells from a 7- to 10-week-old Sipa1^+/+ mouse were sorted by magnetic-activated cell sorting (MACS) and transplanted into sublethally irradiated CD45.2⁺ young (8-10 week old) Sipa1^+/+ and Sipa1^−/− recipient mice. The PB of the recipients was monitored monthly after transplantation. (B) Total donor-derived blood reconstitution in the Sipa1^+/+ and Sipa1^−/− recipients after transplantation. Data are mean ± SEM, from 2 independent experiments, n = 12 Sipa1^+/+ recipients and n = 10 Sipa1^−/− recipients. (C) RBCs, HGB, PLTs, and total WBCs in the recipient PB. The PB was analyzed monthly for monitoring the development of the disorders in the PB of the sublethally irradiated Sipa1^+/+ and Sipa1^−/− recipients after transplantation. (D) Donor-derived WBC and myeloid cells in Sipa1^+/+ and Sipa1^−/− mice after transplantation. (E) Donor-derived B cells, T cells, and natural killer cells in the Sipa1^+/+ and Sipa1^−/− mice after transplantation. (F) H&E staining of PB smears of the Sipa1^+/+ and Sipa1^−/− recipients 9 months after transplantation. Scale bars represent 25 μm. Black arrows indicate microcytes; red arrows indicate macrocytes, and green arrows indicate erythroblasts, respectively. (G) Distribution of reticulocytes, macrocytes, microcytes, spherocytes, erythroblasts, and normal size RBC. (H) Splenomegaly in the Sipa1^−/− recipients 6 to 9 months after transplantation. (I) Enhanced expansion of donor-derived HSPCs in the recipient Sipa1^−/− BM 9 months after transplantation. The donor-derived (CD45.1⁺) HSCs and HPCs were calculated in total BM Lineage (LIN)⁻ cells. *P < .05; **P < .01; ***P < .001, analyzed by unpaired Mann-Whitney U test. See also in supplemental Figure 3.