期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：18
页码：E2281-E2289
DOI：10.1073/pnas.1504407112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceDifferent cells in a clonal population can be in different phenotypic states, which persist for a few generations before switching to another state. Dynamics of switching between these states determines the extent of correlations between the phenotypes of related cells. Here we demonstrate--using ideas from statistical physics--that it is possible to infer simple stochastic dynamics along lineages from an instantaneous measurement of phenotypic correlations in a cell population with defined genealogy. The approach is validated using experimental observations on Pseudomonas aeruginosa colonies. Populations of isogenic embryonic stem cells or clonal bacteria often exhibit extensive phenotypic heterogeneity that arises from intrinsic stochastic dynamics of cells. The phenotypic state of a cell can be transmitted epigenetically in cell division, leading to correlations in the states of cells related by descent. The extent of these correlations is determined by the rates of transitions between the phenotypic states. Therefore, a snapshot of the phenotypes of a collection of cells with known genealogical structure contains information on phenotypic dynamics. Here, we use a model of phenotypic dynamics on a genealogical tree to define an inference method that allows extraction of an approximate probabilistic description of the dynamics from observed phenotype correlations as a function of the degree of kinship. The approach is tested and validated on the example of Pyoverdine dynamics in Pseudomonas aeruginosa colonies. Interestingly, we find that correlations among pairs and triples of distant relatives have a simple but nontrivial structure indicating that observed phenotypic dynamics on the genealogical tree is approximately conformal--a symmetry characteristic of critical behavior in physical systems. The proposed inference method is sufficiently general to be applied in any system where lineage information is available.
