Erythropoiesis is a complex multistage process for the differentiation of mature erythrocytes from hematopoictic stem cells. The function of several transcription factors has been reported in hernatopoictic stem cell differentiation. However, the molecular basis governing its functional behavior is unclear. In this study, we characterized the role of Zfpm-1 during the erythropoietic differentiation of human hernatopoietic stem cells. To verify the function of 4fpm-1 during erythropoietic differentiation, we established human CD34(+) cell culture system by using human umbilical cord blood. At day 7 of the human CD34(+) cell differentiation process to proerythocytes, Zfpm-1 was initially up-regulated and then dramatically down-regulated at day 9. The Zfpm-1 siRNA transfected HSCs contained 20% more GPA(+) cells than the mock transfected cells, and showed repressed expression of the hernatopoietic transcription factors, c-myc and c-myb, but increased expression of GATA-1. In contrast, the Zfpm-1 gain-of-function is the opposite of loss-of-function results above. (c) 2006 Elsevier Inc. All rights reserved.