Self-renewal and differentiation of a basic fibroblast growth factor-dependent multipotent hematopoietic cell line derived from embryonic stem cells

Despite the accumulation of information on the origin of hematopoietic stem cells, it is still unclear how these cells are generated in ontogeny. isol ation of cell lines equivalent to early embryonic hematopoietic progenitor cells can be helpful. A multipotent hematopoietic progenitor cell line, A-6 , was isolated from H-1 embryonic stem (ES) cells. The self-renewal of A-6 cells was supported by basic-fibroblast growth factor (b-FGF) and their dif ferentiation into definitive erythroid cells, granulocytes and macrophages was induced after cc-culture with ST-2 stromal cells. A-6 cells were positi ve for the surface markers of hematopoietic stem cell, c-kit, CD31, CD34, F lt3/Flk2, PgP-1, and HSA, but were negative for that of the differentiated cells. Reverse transcription-polymerase chain reaction analysis showed that A-6 cells produced mRNA from SCL/tal-1 and GATA-2 genes. Among various cyt okines examined, only stem cell factor (SCF) and Flt3/Flk2 ligand (FL) supp orted the proliferation of A-6 cells instead of b-FGF. The FL, as well as b -FGF, supported the self-renewal of A-6 cells, whereas SCF induced differen tiation into myeloid cells. A-6 cells will be useful for the characterizati on of hematopoietic progenitor cells derived from ES cells and provide a mo del system to realize the control mechanisms between self-renewal and diffe rentiation of hematopoietic stem cells.