Related papers: Reconstructing an epigenetic landscape using a gen…
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…
We propose a physical model for developmental process at cellular level to discuss the mechanism of epigenetic landscape. In our simplified model, a minimal model, the network of the interaction among cells generates the landscape…
Maintaining tissue homeostasis requires appropriate regulation of stem cell differentiation. The Waddington landscape posits that gene circuits in a cell form a potential landscape of different cell types, wherein cells follow attractors of…
One of the fundamental cellular processes governed by genetic regulatory networks in cells is the transition among different states under the intrinsic and extrinsic noise. Based on a two-state genetic switching model with positive…
Stochastic simulation has been a powerful tool for studying the dynamics of gene regulatory networks, particularly in terms of understanding how cell-phenotype stability and fate-transitions are impacted by noisy gene expression. However,…
Cells can often choose among several stably heritable phenotypes. Examples are the expression of genes in eukaryotic cells where long chromosomal regions can adopt persistent and heritable silenced or active states, that may be associated…
Understanding how gene regulatory networks (GRNs) give rise to stable and dynamic cellular states remains a central challenge in theoretical biology, particularly when slow epigenetic feedback reshapes the underlying regulatory landscape.…
Gene regulatory network (GRN) modeling is a well-established theoretical framework for the study of cell-fate specification during developmental processes. Recently, dynamical models of GRNs have been taken as a basis for formalizing the…
We use large deviation methods to calculate rates of noise-induced transitions between states in multistable genetic networks. We analyze a synthetic biochemical circuit, the toggle switch, and compare the results to those obtained from a…
Reprogramming is a process of transforming differentiated cells into pluripotent stem cells by inducing specific modifying factors in the cells. Reprogramming is a non-equilibrium process involving a collaboration at levels separated by…
Epistasis describes the phenomenon that mutations at different loci do not have independent effects with regard to certain phenotypes. Understanding the global epistatic landscape is vital for many genetic and evolutionary theories. Current…
Developmental dynamics of multicellular organism is a process that takes place in a multi-stable system in which each attractor state represents a cell type and attractor transitions correspond to cell differentiation paths. This new…
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…
Statistical physics provides a useful perspective for the analysis of many complex systems; it allows us to relate microscopic fluctuations to macroscopic observations. Developmental biology, but also cell biology more generally, are…
Biological structure and function depend on complex regulatory interactions between many genes. A wealth of gene expression data is available from high-throughput genome-wide measurement technologies, but effective gene regulatory network…
How do mammalian cells that share the same genome exist in notably distinct phenotypes, exhibiting differences in morphology, gene expression patterns, and epigenetic chromatin statuses? Furthermore how do cells of different phenotypes…
Free energy landscapes encode the kinetics, intermediates, and transition states that govern molecular processes and are thus a key target of single biomolecule research. Typical approaches to deriving optimal, error-minimizing,…
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…
We propose a minimal model to simulate long waiting times followed by evolutionary bursts on rugged landscapes. It combines point and inversions-like mutations as sources of genetic variation. The inversions are intended to simulate one of…
Characterization of pluripotent states, in which cells can both self-renew and differentiate, and the irreversible loss of pluripotency are important research areas in developmental biology. In particular, an understanding of these…