Control of cell differentiation during proliferation. I. Monocytic differentiation of HL-60 promyelocytes.
The cell proliferation relating an uncommitted precursor cell to a differentiated terminal cell has been quantitated. HL-60 promyelocytes, a bipotent precursor cell capable of differentiating along either the myeloid or monocytic pathway, were induced by a human lymphocyte-conditioned medium (CM) to differentiate into macrophage-like cells. The promyelocytes had a generation time of approx. 42 h. Most promyelocytes which differentiated became macrophage-like cells after only one cell division. Some, a minority, underwent more than one division. The time between induction of differentiation and expression of differentiated characteristics could thus be very short. Labelled S-phase promyelocytes could differentiate after traversing S. G2 and undergoing mitosis. Some, approx. 21%, required a subsequent complete cell cycle before differentiating. The data suggest a model in which cells must undergo a S-phase-specific differentiation control event in the presence of CM in order to differentiate in the subsequent G1 phase. This model proposes that a discrete time in S phase exists when cells are susceptible to exogenous regulation directing them to yield differentiated daughter cells.
D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D006801:Humans; D007399:Interphase; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000166:cytology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013997:Time Factors
D010835:Phytohemagglutinins