Upregulation of flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity

Flt3 has emerged as a potential regulator of hematopoietic stem cells (HSC) . Sixty percent of cells in the mouse marrow Lin(-)Sca1(+)c-kit(+) HSC pool expressed fIt3. Although single cell cloning showed comparable high prolif erative, myeloid, B, and T cell potentials of Lin(-)Sca1(+)c-kit(+)flt3(+) and Lin(-)Sca1(+)c-kit(+)flt3(-) cells, only Lin(-)Sca1(+)c-kit(+)flt3(-) c ells supported sustained multilineage reconstitution. In striking contrast, Lin(-)Sca1(+)c-kit(+)fIt3(+) cells rapidly and efficiently reconstituted B and T lymphopoiesis, whereas myeloid reconstitution was exclusively short term. Unlike c-kit, activation of fIt3 failed to support survival of HSC, w hereas only fIt3 mediated survival of Lin(-)Sca1(+)c-kit(+)flt3(+) reconsti tuting cells. Phenotypic and functional analysis support that Lin-Sca1(+)c- kit(+)flt3(+) cells are progenitors for the common lymphoid progenitor. Thu s, upregulation of fIt3 expression on Lin(-)Sca1(+)c-kit(+) HSC cells is ac companied by loss of self-renewal capacity but sustained lymphoid-restricte d reconstitution potential.