ASYMMETRIC CELL DIVISIONS SUSTAIN LONG-TERM HEMATOPOIESIS FROM SINGLE-SORTED HUMAN FETAL LIVER-CELLS

Hematopoietic stem cells (HSCs) in adult marrow are believed to be der ived from fetal liver precursors. To study cell kinetics involved in l ong-term hematopoiesis, we studied single-sorted candidate HSCs fro-fe tal liver that were cultured in the presence of a mixture of stimulato ry cytokines. After 8-10 d, the number of cells in primary cultures va ried from <100 to >10,000 cells. Single cells in slow growing colonies were recloned upon reaching a 100-200 cell stage. Strikingly, the num ber of cells in subclones varied widely again. These results are indic ative of asymmetric divisions in primitive hematopoietic cells in whic h proliferative potential and cell cycle properties are unevenly distr ibuted among daughter cells. The continuous generation of functional h eterogeneity among the clonal progeny of HSCs is in support of intrins ic control of stem cell fate and provides a model for the long-term ma intenance of hematopoiesis in vitro and in vivo.