Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity.

Research output: Contribution to journalJournal articleResearchpeer-review

J Adolfsson, O J Borge, D Bryder, K Theilgaard-Mönch, I Astrand-Grundström, E Sitnicka, Y Sasaki, S E Jacobsen

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.
Original languageEnglish
Issue number4
Pages (from-to)659-69
Number of pages10
Publication statusPublished - 2001
Externally publishedYes

Bibliographical note

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

ID: 5142975