Related papers: Pluripotency, differentiation, and reprogramming: …
Many genes have been identified as driving cellular differentiation, but because of their complex interactions, the understanding of their collective behaviour requires mathematical modelling. Intriguingly, it has been observed in numerous…
A common metaphor for describing development is a rugged "epigenetic landscape" where cell fates are represented as attracting valleys resulting from a complex regulatory network. Here, we introduce a framework for explicitly constructing…
In multicellular organisms, cells differentiate into several distinct types during early development. Determination of each cellular state, along with the ratio of each cell type, as well as the developmental course during cell…
The evolutionary origins of structural features in reconstructed gene-regulatory networks (GRNs) remain poorly understood, especially given the random aspects of gene expression. Here, we extend a classical model of GRN evolution to allow a…
Tumorigenic transformation of human epithelial cells in vitro has been described experimentally as the potential result of a process known as spontaneous immortalization. In this process a generic series of cell state transitions occur in…
Systems biology approaches combining theoretical modeling with experiments have been singularly successful in uncovering novel features of cellular phenomena. One such feature is that of binary gene expression in which the expression level…
Precise temporal coordination of gene expression is crucial for many developmental processes. One central question in developmental biology is how such coordinated expression patterns are robustly controlled. During embryonic development of…
Cell type (e.g. pluripotent cell, fibroblast) is the end result of many complex processes that unfold due to evolutionary, developmental, and transformational stimuli. A cell's phenotype and the discrete, a priori states that define various…
Based on the measurements of noise in gene expression performed during the last decade, it has become customary to think of gene regulation in terms of a two-state model, where the promoter of a gene can stochastically switch between an ON…
A dynamic model for cell differentiation is studied, where cells with internal chemical reaction dynamics interact with each other and replicate. It leads to spontaneous differentiation of cells and determination, as is discussed in the…
The two most fundamental processes describing change in biology, development and evolu-tion, occur over drastically different timescales, difficult to reconcile within a unified framework. Development involves temporal sequences of cell…
To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein…
A single gene, regulating its own expression via a positive feedback loop, constitutes a common motif in gene regulatory networks and signalling cascades. Recent experiments on the development of competence in the bacterial population…
Cell functional diversity is a significant determinant on how biological processes unfold. Most accounts of diversity involve a search for sequence or expression differences. Perhaps there are more subtle mechanisms at work. Using the…
Epigenetic modifications to histones may promote either activation or repression of the transcription of nearby genes. Recent experimental studies show that the promoters of many lineage-control genes in stem cells have "bivalent domains"…
Interactions between genes and gene products give rise to complex circuits that enable cells to process information and respond to external signals. Theoretical studies often describe these interactions using continuous, stochastic, or…
Understanding the rules underlying organismal development is a major unsolved problem in biology. Each cell in a developing organism responds to signals in its local environment by dividing, excreting, consuming, or reorganizing, yet how…
Morphogenesis of complex body shapes is reproducible despite the noise inherent in the underlying morphogenetic processes. However, how these morphogenetic processes work together to achieve this reproducibility remains unclear. Here, we…
From the response to external stimuli to cell division and death, the dynamics of living cells is based on the expression of specific genes at specific times. The decision when to express a gene is implemented by the binding and unbinding…
We study genetic networks that produce many species of non-coding RNA molecules that are present at a moderate density, as typically exists in the cell. The associations of the many species of these RNA are modeled physically, taking into…