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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 flt3. Although single cell cloning showed comparable high proliferative, 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(-) cells supported sustained multilineage reconstitution. In striking contrast, Lin(-)Sca1(+)c-kit(+)flt3(+) cells rapidly and efficiently reconstituted B and T lymphopoiesis, whereas myeloid reconstitution was exclusively short term. Unlike c-kit, activation of flt3 failed to support survival of HSC, whereas only flt3 mediated survival of Lin(-)Sca1(+)c-kit(+)flt3(+) reconstituting cells. Phenotypic and functional analysis support that Lin(-)Sca1(+)c-kit(+)flt3(+) cells are progenitors for the common lymphoid progenitor. Thus, upregulation of flt3 expression on Lin(-)Sca1(+)c-kit(+) HSC cells is accompanied by loss of self-renewal capacity but sustained lymphoid-restricted reconstitution potential.

Type

Journal article

Journal

Immunity

Publication Date

10/2001

Volume

15

Pages

659 - 669

Keywords

Animals, Cell Differentiation, Cell Lineage, Cell Survival, Cells, Cultured, Hematopoiesis, Hematopoietic Stem Cells, Kinetics, Lymphocytes, Membrane Proteins, Mice, Myeloid Progenitor Cells, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-kit, RNA, Messenger, Receptor Protein-Tyrosine Kinases, Stem Cell Factor, Up-Regulation, fms-Like Tyrosine Kinase 3