Overexpression of p21 Has Inhibitory Effect on Human Hematopoiesis by Blocking Generation of CD43+ Cells via Cell-Cycle Regulation

BACKGROUND AND OBJECTIVES: p21, an important member of the Cip/Kip family, is involved in inhibitory effects of RUNX1b overexpression during the early stage of human hematopoiesis. METHODS AND RESULTS: We established a human embryonic stem cell (hESC) line with inducible expression of p21 (p21/hESCs). Overexpression of p21 did not influence either mesoderm induction or emergence of CD34+ cells, but it significantly decreased the production of CD43+ cells and changed the expression profile of hematopoiesis-related factors, leading to the negative effects of p21 on hematopoiesis. CONCLUSIONS: In RUNX1b/hESC co-cultures when RUNX1b was induced from D0, perturbation of the cell cycle caused by upregulation of p21 probably prevented the appearance of CD43+ cells, but not CD34+ cells. The mechanisms via which CD34+ cells are blocked by RUNX1b overexpression remain to be elucidated.