Signaling from fibroblast growth factor receptor 2 in immature hematopoietic cells facilitates donor hematopoiesis after intra-bone marrow-bone marrow transplantation

Stem Cells Dev. 2010 Nov;19(11):1679-86. doi: 10.1089/scd.2009.0370. Epub 2010 Sep 10.

Abstract

Fibroblast growth factor (FGF) and FGF receptor (FGFR) are expressed in various cells including endothelial progenitor cells and hematopoietic cells. The interaction between FGF and FGFR is associated with the proliferation, migration, and survival of these cells. In this report, we examined the effects of FGFR2 signaling on hematopoiesis in immature hematopoietic cells, using mutant mice in which a constitutively active form of FGFR2 mutant was caused to be overexpressed by the Tie2 promoter (FGFR2 Tg mice). Under normal conditions, hematopoiesis of FGFR2 Tg mice and wild type (Wt) mice do not differ significantly, except for the weight and cell numbers of the thymus. However, the c-kit(+)Sca-1(+)lineage⁻ bone marrow cells (BMCs) of FGFR2 Tg mice facilitate the formation of colony-forming units of culture. When these BMCs were transplanted into the recipient bone marrow (intra-bone marrow-bone marrow transplantation), there was better reconstitution of donor hematopoietic cells. In the in vitro experiment, the c-kit(+)Sca-1(+)lineage⁻ BMCs from FGFR2 Tg mice showed fewer apoptotic cells than those from Wt mice. These results suggest that the antiapoptotic effect of FGFR2 signaling facilitates the hematopoiesis of FGFR2 Tg mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / genetics
  • Antigens, Ly / metabolism
  • Bone Marrow Transplantation / methods*
  • Cell Lineage
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • RNA, Messenger / metabolism
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
  • Signal Transduction / physiology*

Substances

  • Antigens, Ly
  • Ly6a protein, mouse
  • Membrane Proteins
  • RNA, Messenger
  • Proto-Oncogene Proteins c-kit
  • Receptor, Fibroblast Growth Factor, Type 2