The concept of G0 cells was introduced by Laitha four decades ago, initially as an operational term, to define the cells which do not enter S phase for the duration of at least two cell cycles. Since then there is constant confusion as to whether such cells are actually having long G1 or are "genuine G0" cells such as expected in the case of nonproliferationg stem cells, and whether metabolic or other markers to distinguish G0 from G1 cells exist. The first such marker was shown to be cellular RNA content, or number of ribosomes per cell: quiescent, G0 cells, contain on average 10 times fewer ribosomes compared to cycling G1 cells (e.g. Stanners et al., J. Cell Physiol, 11: 127, 1979), and much less of total RNA, as measured by flow cytometry (PNAS, 73: 2881, 1976). In contrast to normal cells (nonstimulated lymphocytes, fibroblasts maintained in absence of growth factors) most tumor and transformed cell lines do not enter a state which is characterized by such low RNA content. By the criterium of RNA content, transformed cells rather die than enter G0. Another marker which appears to distinguish G0 cells is the lack of cyclins D (and cyclin E) expression (e.g. Cytometry, 25: 1, 1996). Here again, most tumor lines appear to have different pattern of cyclins D expression compared to normal cells, which precludes identification of G0 cells in these lines. The pattern of expression of Ki-67 is more complex: while G0 cells are Ki-67 negative, also negative appears to be a cohort of G1 cells just prior to entrance to S. Zbigniew Darzynkiewicz
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