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Lymphoid-primed multipotent progenitors with down-regulated megakaryocyte-erythroid (MkE) potential are restricted to cells with high levels of cell-surface FLT3 expression, whereas HSCs and MkE progenitors lack detectable cell-surface FLT3. These findings are compatible with FLT3 cell-surface expression not being detectable in the fully multipotent stem/progenitor cell compartment in mice. If so, this process could be distinct from human hematopoiesis, in which FLT3 already is expressed in multipotent stem/progenitor cells. The expression pattern of Flt3 (mRNA) and FLT3 (protein) in multipotent progenitors is of considerable relevance for mouse models in which prognostically important Flt3 mutations are expressed under control of the endogenous mouse Flt3 promoter. Herein, we demonstrate that mouse Flt3 expression initiates in fully multipotent progenitors because in addition to lymphoid and granulocyte-monocyte progenitors, FLT3(-) Mk- and E-restricted downstream progenitors are also highly labeled when Flt3-Cre fate mapping is applied.

Original publication

DOI

10.1182/blood-2010-10-316232

Type

Journal article

Journal

Blood

Publication Date

08/2011

Volume

118

Pages

1544 - 1548

Addresses

Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Keywords

Monocytes, Bone Marrow Cells, Granulocyte Precursor Cells, Hematopoietic Stem Cells, Cell Membrane, Multipotent Stem Cells, Animals, Mice, Inbred C57BL, Mice, Transgenic, Humans, Mice, Luminescent Proteins, Bone Marrow Transplantation, Flow Cytometry, Gene Expression Profiling, Reverse Transcriptase Polymerase Chain Reaction, Cell Lineage, fms-Like Tyrosine Kinase 3, Erythroid Precursor Cells, Megakaryocyte Progenitor Cells