G0/G1 discrimination
ZBIGNIEW DARZYNKIEWICZ (darzynk@nymc.edu)
Sun, 02 Feb 1997 10:49:51 -0500
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