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

Summary, in English

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.

• Författare: Jörgen Adolfsson; O J Borge; David Bryder; K Theilgaard-Monch; Ingbritt Åstrand-Grundström; Ewa Sitnicka Quinn; Yutaka Sasaki; Sten Eirik W Jacobsen
• Avdelning/ar: Stamcellscentrum (SCC); Immunology
• Publiceringsår: 2001
• Språk: Engelska
• Sidor: 659-669
• Publikation/Tidskrift/Serie: Immunity
• Volym: 15
• Issue: 4
• Länkar: http://dx.doi.org/10.1016/S1074-7613(01)00220-5
• Dokumenttyp: Artikel i tidskrift
• Förlag: Cell Press
• Ämne: Immunology in the medical area
• Status: Published
• Forskningsgrupp: Immunology
• ISBN/ISSN/Övrigt: ISSN: 1074-7613