Extended Data Fig. 7: Enhanced susceptibility of HSCs to necroptosis during aging.
From: Aging-induced MCPH1 translocation activates necroptosis and impairs hematopoietic stem cell function
(a) The images show morphological alteration of in Mlkl−/− and WT HSCs at young (3 months) and old (29 months) age. (b) The scatter plots depict the percentage of necroptotic cell death in Mlkl−/− and WT HSCs at young (3 months) and old (29 months) age. Data were shown as mean ± SD. Statistical significance was measured by two-way ANOVA followed by Tukey’s test for post hoc comparison. n = 3 independent experiments. (c-f) KSL cells were freshly isolated from young (5 months) or old (18 months) mice were infected by lentivirus carrying the cDNA of WT MCPH1 or MCPH1- K348R-K350R-K360R-K362R mutant (MCPH14KR), and 72 hours later, 2 × 104 GFP+ cells were sorted and injected into lethally irradiated recipients together with 2 × 105 competitor cells. Peripheral blood of recipient mice was evaluated every month until the 4th month. This histogram displays the percentage of GFP+ cell in overall (CD45.2+), B (B220+), T (CD3+) and myeloid (Mac-1+) cell every month after transplantation. n = 6-7 mice per group (n = 6 for Young: Vector, Young: MCPH1-WT, Old: Vector, and Old: MCPH1-WT; n = 7 for Young: MCPH1-4KR and Old: MCPH1-4KR), data were shown as mean ± SD. Two-tailed unpaired Student’s t-test was used for statistical analysis.
