Correlation of c-kit expression and cell cycle regulation by transforming growth factor-beta in CD34+ CD38- human bone marrow cells

Eur J Haematol. 2003 Nov;71(5):351-8. doi: 10.1034/j.1600-0609.2003.00152.x.

Abstract

To investigate the relationship between c-kit expression and cell cycle regulation by endogenous transforming growth factor-beta (TGF-beta) in human bone marrow hematopoietic progenitor cells, CD34+ CD38- c-kit(low/-) and CD34+ CD38- c-kit(high) populations were cultured in stem cell factor, thrombopoietin, interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor, granulocyte/macrophage colony-stimulating factor and anti-TGF-beta, and analyzed for cell cycle status. Arrest in G0/G1 was most prominent in the precultured CD34+ CD38- c-kit(low/-) subset (95.62 +/- 4.15%). While postcultured CD34+ CD38- c-kit(high) cells initiated from CD34+ CD38- c-kit(high) cells entered cell cycle within 36 hr, postcultured CD34+ CD38- c-kit(low/-) cells initiated from CD34+ CD38- c-kit(low/-) cells remained dormant until 36 hr and entered cell cycle within 90 hr. Anti-TGF-beta increased the percentage of S/G2M phase postcultured CD34+ CD38- c-kit(high) cells (from 19.08 +/- 11.95 to 47.04 +/- 2.93%), but no significant change was observed in postcultured CD34+ CD38- c-kit(low/-) cells. These results suggest that endogenous TGF-beta plays an important role in the cell cycle arrest of c-kit(high) but not c-kit(low/-) cells in CD34+ CD38- cells, which proliferate without undergoing differentiation. The different regulatory mechanism of cell cycle entry of the CD34+ CD38- c-kit(high) and CD34+ CD38- c-kit(low/-) subsets might be the result of differences in their sensitivity to endogenous TGF-beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / analysis
  • ADP-ribosyl Cyclase 1
  • Adult
  • Antigens, CD / analysis
  • Antigens, CD34 / analysis
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Cell Cycle / drug effects*
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Culture Media, Serum-Free / pharmacology
  • Cytokines / pharmacology
  • Gene Expression Regulation / drug effects*
  • Hematopoietic Cell Growth Factors / pharmacology
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-kit / biosynthesis*
  • Proto-Oncogene Proteins c-kit / genetics
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta / physiology

Substances

  • Antigens, CD
  • Antigens, CD34
  • Culture Media, Serum-Free
  • Cytokines
  • Hematopoietic Cell Growth Factors
  • Membrane Glycoproteins
  • Transforming Growth Factor beta
  • Proto-Oncogene Proteins c-kit
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1