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Biology subjects

Marr, C.

Publications and source records attributed to Marr, C..

2 recordsLinked to original sources

Parameter inference with analytical propagators for stochastic models of autoregulated gene expression

Stochastic gene expression in regulatory networks is conventionally modelled via the Chemical Master Equation (CME). As explicit solutions to the CME, in the form of so-called propagators, are oftentimes not readily available, various approximations have been proposed. A recently developed analytical method is based on a separation of scales that assumes significant differences in the lifetimes of mRNA and protein in the network, allowing for the efficient approximation of propagators from asymptotic expansions for the corresponding generating functions. Here, we showcase the applicability of that method to simulated data from a telegraph model for gene expression that is extended with an autoregulatory mechanism. We demonstrate that the resulting approximate propagators can be applied successfully for Bayesian parameter inference in the non-regulated model; moreover, we show that, in the extended autoregulated model, autoactivation or autorepression may be refuted under certain assumptions on the model parameters. Our results indicate that the method showcased here may allow for successful parameter inference and model identification from longitudinal single cell data.

cell biology

Subtle Changes in Clonal Dynamics Underlie the Age-Related Decline in Neurogenesis

Neural stem cells in the adult murine brain have only a limited capacity to self-renew, and the number of neurons they generate drastically declines with age. How cellular dynamics sustain neurogenesis and how alterations with age may result in this decline, are both unresolved issues. Therefore, we clonally traced neural stem cell lineages using confetti reporters in young and old adult mice. To understand underlying mechanisms, we derived mathematical population models of adult neurogenesis that explain the observed clonal cell type abundances. Models fitting the data best consistently show self renewal of transit amplifying progenitors and rapid neuroblast cell cycle exit. Most importantly, we identified an increase of asymmetric stem cell divisions at the expense of symmetric stem cell differentiation with age. Beyond explaining existing longitudinal population data, our model identifies a particular cellular strategy underlying adult neural stem cell homeostasis that gives insights into the aging of a stem cell compartment.

neuroscience