Transforming growth factor-β regulates the cell cycle status of interleukin-3 (IL-3) plus IL-1, stem cell factor, or IL-6 stimulated CD34+ human hematopoietic progenitor cells through different cell kinetic mechanisms depending on the applied stimulus

F. Lardon, H. W. Snoeck, T. G. Nijs, M. Lenjou, M. E. Peetermans, I. Rodrigus, Z. N. Berneman, D. R.V. Bockstaele

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31 Scopus citations

Abstract

The immediate cell kinetic response of highly purified human bone marrow progenitor cells (CD34+ sorted fraction) to the inhibitory effects of transforming growth factor-β (TGF-β) was studied using the BrdU-Hoechst flow-cytometric technique. The progenitor cells were stimulated with either interleukin-3 (IL-3) alone or with IL-3 in combination with IL-1, stem cell factor (SCF), or IL-6, and the inhibitory action of TGF-β was evaluated in each phase of the first three consecutive cell cycles. Semisolid methylcellulose cultures were also performed to compare these initial events to the effects observed after 7, 14, and 21 days of incubation. Within the CD34+ compartment, the progenitor cells fan be discriminated on a functional basis, i.e., in terms of TGF-β sensitivity. Very primitive progenitors, recruited out of the. G0 phase by IL-3 plus an early-acting factor (IL-1, SCF) are, upon addition of TGF-β, arrested specifically in the G, phase of the second cell cycle. In the clonogenic assays, the increased colony formation due to IL-1 or SCF was completely abolished by the counteracting effect of TGF-β that diminished colony output back to the level of TGF-β-plus-IL-3 supplemented colony growth. Addition of TGF-β to CD34+ progenitors responding to IL-3 alone resulted in an overall retardation, but without an apparent specific accumulation of cells in any of the cell cycles. Finally, within the CD34+ compartment, there exists a subset of IL-3-responsive, but TGF-β-insensitive, progenitor cells that were, upon addition of TGF-β, not arrested at all. In conclusion, our results demonstrate that TGF-β exerts different cell kinetic effects on CD34+ progenitor cell growth depending on the applied stimulus.

Original languageEnglish
Pages (from-to)903-909
Number of pages7
JournalExperimental Hematology
Volume22
Issue number9
StatePublished - 1994
Externally publishedYes

Keywords

  • CD34
  • Cell cycle kinetics
  • Hematopoiesis
  • Transforming growth factor-β

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