Seric factors influence cell cycle modifications during commitment of murine erythroleukemia cells to differentiation

Abstract

Cell cycle modifications are among the early events which take place during the induced differentiation of murine erythroleukemia (MEL) cells; a transient accumulation of the cells in the G , phase of the cell cycle, followed by a re-entry of the cells into a proliferation state, has been described. In order to characterize a putative role of serum in such variations, we have studied the modifications of the cell cycle parameters when cells were induced to differentiate in the presence or in the absence of seric factors. We show that, in the absence of exogenous factors brought by serum, the G, accumulation was enhanced both in amplitude and in duration, but cells were still able to bypass the G , block and re-enter into the S phase. These results indicate that the resumption of cell proliferation after the transient block is under synergistic control of seric and endogenous factors, but these later are sufficient to overcome the block. However, MEL cells were unable to differentiate in the absence of seric factors, as measured by the number of bemidine-positive cells during induction with hexamethylene-bisacetamide (HMBA) or butyric acid. This capacity to differentiate was recovered when serum was added back to the culture medium, and the efficiency of recovery was maximal when cells underwent a full round of DNA replication in the presence of serum after the GI block. The analysis of two molecular markers of cell differentiation confirmed these results. 0 1992 Wiley-Liss, Inc.

The potential role of ribosomal protein S5 on cell cycle arrest and initiation of murine erythroleukemia cell differentiation

“…This is an interesting observation suggesting that commitment decisions may be coupled with limitation of proliferation potential by the combined function of specific cytoplasmic factors in accordance with external stimuli brought by inducers of differentiation. The latter, must be also seen as a possibility in light of evidence showing that the transient accumulation of MEL cells in the G 1 phase of the cell cycle upon initiation of differentiation is followed by a re-entry of cells into a proliferative state, processes that are under the control of exogenous factors present in the serum and their endogenous cytoplasmic counterparts [Mencherini et al, 1992]. The question whether the delay in the onset of erythroid differentiation is attributed to constitutive expression of RPS5 gene among other events needs extensive investigation by applying small interfering…”