Long-term engraftment ability and multipotent differentiation capacity of compound-mutant HSCs. BM MNCs (CD45.2+) were collected separately from each genotype of mice before Tak1 deletion was induced. These BM cells were mixed with competitor BM MNCs (CD45.1+) in a 10:1 ratio and transplanted into lethally-irradiated recipient mice (CD45.1+). Each recipient mouse received 2 × 106 BM MNCs of the indicated genotype and 2 × 105 competitor BM cells. One month after transplantation, the contribution of donor cells to hematopoiesis in recipient mice was examined by analyzing the percentage of CD45.2+ cells in their PB. Mice were then injected with poly I:C every other day for a total of 3 injections to induce Tak1 deletion. The donor cell contribution to recipients' PB composition was analyzed on day 10 and day 20 (A), as well as 3 months (B) after poly I:C injections. (C) The myeloid and lymphocyte differentiation of Tak1−/−Tnfr1−/− and Tak1−/−Tnfr1−/−r2−/− HSPCs was analyzed 3 months after the induction of Tak1 deletion. **Significant reduction compared with WT control group (P < .01). $$Significant increase compared with Tak1−/− group (P < .01).