To investigate the maturation of neonatal erythrocytes and kinetics of globin expression, we induced CD34(+) cells purified from human umbilical cord blood to erythroid differentiation in different suspension culture systems containing human cord serum (CHS) and adult serum (AHS), respectively. The zeta- to alpha-globin switching and the epsilon- to gamma-globin switching were observed in CHS+ cultures but not in AHS(+) cultures. A reduced proportion of F cell and two day postponed cell enucleation in AHS+ cultures compared with in CHS+ cultures was also found. However, predominant gamma-globin expression compared with epsilon- and beta-globin was always observed from days 5 in either CHS+ or AHS(+) cultures. Our data showed that neonatal erythrocytes in CHS+ cultures maintained their fetal characteristics which differed from their counterpart from adult. Serum from different developmental stage significantly affected the maturation and globin expression pattern of cultured neonatal erythrocytes. Obviously, some uncertain serum components play important roles in cultures, but they are not enough to fundamentally change the developmentally specific globin gene transcription program, suggesting that this program is mainly controlled by determinants within the erythroid progenitors. (c) 2005 Elsevier Inc. All rights reserved.