摘要：Deficiency of
P18 can significantly improve the self-renewal potential of hematopoietic stem cells (HSC) and the success of long-term engraftment. However, the effects of
P18 overexpression, which is involved in the inhibitory effects of
RUNX1b at the early stage of hematopoiesis, have not been examined in detail. In this study, we established inducible
P18/hESC lines and monitored the effects of
P18 overexpression on hematopoietic differentiation. Induction of
P18 from day 0 (D0) dramatically decreased production of CD34
highCD43− cells and derivative populations, but not that of CD34
lowCD43− cells, changed the cell cycle status and apoptosis of KDR+ cells and downregulated the key hematopoietic genes at D4, which might cause the severe blockage of hematopoietic differentiation at the early stage. By contrast, induction of
P18 from D10 dramatically increased production of classic hematopoietic populations and changed the cell cycle status and apoptosis of CD45+ cells at D14. These effects can be counteracted by inhibition of TGF-β or NF-κB signaling respectively. This is the first evidence that
P18 promotes hematopoiesis, a rare property among cyclin-dependent kinase inhibitors (CKIs).
