Extended Data Fig. 5: Targeted dysfunction of necroptosis signaling ameliorates HSCs.
From: Age-related noncanonical TRMT6–TRMT61A signaling impairs hematopoietic stem cells
(a-b) 10 HSCs from 5-month old Ripk1K45A or WT mice were transplanted into recipients together with 3×105 competitor cells. (a) Percentage of donor cell reconstitution in overall, B, T and myeloid cell every month after transplantation. (b) The lineage distribution of donor-derived peripheral blood at the 3rd month. n = 5 mice per group. (c-d) Secondary transplantation assay for Ripk1K45A HSC. (c) Percentage of donor cell reconstitution in overall, B, T and myeloid cell every month after transplantation. (d) The lineage distribution of donor-derived peripheral blood at the 3rd month. n = 6-7 mice per group (WT: n = 6; Ripk1K45A: n = 7). (e-f) 20 HSCs from 2 months old Ripk3-/- or WT mice were transplanted into recipients together with 6×105 competitor cells. (e) Percentage of donor cell reconstitution in overall, B, Tand myeloid cell every month after transplantation. (f) The lineage distribution of donor-derived peripheral blood at the fourth month. n = 6-7 mice per group (WT: n = 6; Ripk3-/-: n = 7). (g-h) 20 HSCs from either 5-month old Mlkl-/- or WT mice were transplanted into recipients together with 3×105 competitor cells. (g) Percentage of donor cell reconstitution in overall, B, T and myeloid cell every month after transplantation. (h) The lineage distribution of donor-derived peripheral blood at the 4th month. n = 5-6 mice per group (WT: n = 5; Mlkl-/-: n = 6). (i) 20 HSCs from 5 months old Mlkl-/- or WT mice were transplanted into recipients together with 3×105 competitor cells. Four months after, two million bone marrow cells of primary recipients were transplanted into secondary recipients. Three months after, 50 HSCs isolated from secondary recipients were transplanted into the tertiary recipients together with 3×105 competitor cells. These line plots display the percentage of donor cell reconstitution in overall, B, T and myeloid cell every month after transplantation. n = 5-6 mice per group (WT: n = 6; Mlkl-/-: n = 5). Two-tailed unpaired Student’s t-test was used for statistical analysis in c, e and i. Data are shown as the mean ± SD in a-i.
