TY - JOUR
T1 - Phenotypic variability of growing cellular populations
AU - Lu, Ting
AU - Shen, Tongye
AU - Bennett, Matthew R.
AU - Wolynes, Peter G.
AU - Hasty, Jeff
PY - 2007/11/27
Y1 - 2007/11/27
N2 - The dynamics and diversity of proliferating cellular populations are governed by the interplay between the growth and death rates among the various phenotypes within a colony. In addition, epigenetic multistability can cause cells to spontaneously switch from one phenotype to another. By examining a generalized form of the relative variance of populations and classifying it into intracolony and cross-colony contributions, we study the origins and consequences of cellular population variability. We find that the variability can depend highly on the initial conditions and the constraints placed on the population by the growth environment. We construct a two-phenotype model system and examine, analytically and numerically, its time-dependent variability in both unbounded and population-limited growth environments. We find that in unbounded growth environments the overall variability is strictly governed by the initial conditions. In contrast, when the overall population is limited by the environment, the system eventually relaxes to a unique fixed point regardless of the initial conditions. However, the transient decay to the fixed point depends highly on initial conditions, and the time scale over which the variability decays can be very long, depending on the intrinsic time scales of the system. These results provide insights into the origins of population variability and suggest mechanisms in which variability can arise in commonly used experimental approaches.
AB - The dynamics and diversity of proliferating cellular populations are governed by the interplay between the growth and death rates among the various phenotypes within a colony. In addition, epigenetic multistability can cause cells to spontaneously switch from one phenotype to another. By examining a generalized form of the relative variance of populations and classifying it into intracolony and cross-colony contributions, we study the origins and consequences of cellular population variability. We find that the variability can depend highly on the initial conditions and the constraints placed on the population by the growth environment. We construct a two-phenotype model system and examine, analytically and numerically, its time-dependent variability in both unbounded and population-limited growth environments. We find that in unbounded growth environments the overall variability is strictly governed by the initial conditions. In contrast, when the overall population is limited by the environment, the system eventually relaxes to a unique fixed point regardless of the initial conditions. However, the transient decay to the fixed point depends highly on initial conditions, and the time scale over which the variability decays can be very long, depending on the intrinsic time scales of the system. These results provide insights into the origins of population variability and suggest mechanisms in which variability can arise in commonly used experimental approaches.
KW - Cellular population diversity
KW - Gene noise
KW - Phenotyic variation
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U2 - 10.1073/pnas.0706115104
DO - 10.1073/pnas.0706115104
M3 - Article
C2 - 18025471
AN - SCOPUS:37749050490
SN - 0027-8424
VL - 104
SP - 18982
EP - 18987
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 48
ER -