Incorporating stochastic gene expression, signaling-mediated intercellular interactions, and regulated cell proliferation in models of coordinated tissue development

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Hauptverfasser: Barkan, Casey O., Chou, Tom
Format: Preprint
Veröffentlicht: 2025
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author Barkan, Casey O.
Chou, Tom
author_facet Barkan, Casey O.
Chou, Tom
contents Formulating quantitative and predictive models for tissue development requires consideration of the complex, stochastic gene expression dynamics, its regulation via cell-to-cell interactions, and cell proliferation. Including all of these processes into a practical mathematical framework requires complex expressions that are difficult to interpret and apply. We construct a simple theory that incorporates intracellular stochastic gene expression dynamics, signaling chemicals that influence these dynamics and mediate cell-cell interactions, and cell proliferation and its accompanying differentiation. Cellular states (genetic and epigenetic) are described by a Waddington vector field that allows for non-gradient dynamics (cycles, entropy production, loss of detailed balance) which is precluded in Waddington potential landscape representations of gene expression dynamics. We define an epigenetic fitness landscape that describes the proliferation of different cell types, and elucidate how this fitness landscape is related to Waddington's vector field. We illustrate the applicability of our framework by analyzing two model systems: an interacting two-gene differentiation process and a spatiotemporal organism model inspired by planaria.
format Preprint
id arxiv_https___arxiv_org_abs_2501_11271
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Incorporating stochastic gene expression, signaling-mediated intercellular interactions, and regulated cell proliferation in models of coordinated tissue development
Barkan, Casey O.
Chou, Tom
Cell Behavior
Molecular Networks
Tissues and Organs
Formulating quantitative and predictive models for tissue development requires consideration of the complex, stochastic gene expression dynamics, its regulation via cell-to-cell interactions, and cell proliferation. Including all of these processes into a practical mathematical framework requires complex expressions that are difficult to interpret and apply. We construct a simple theory that incorporates intracellular stochastic gene expression dynamics, signaling chemicals that influence these dynamics and mediate cell-cell interactions, and cell proliferation and its accompanying differentiation. Cellular states (genetic and epigenetic) are described by a Waddington vector field that allows for non-gradient dynamics (cycles, entropy production, loss of detailed balance) which is precluded in Waddington potential landscape representations of gene expression dynamics. We define an epigenetic fitness landscape that describes the proliferation of different cell types, and elucidate how this fitness landscape is related to Waddington's vector field. We illustrate the applicability of our framework by analyzing two model systems: an interacting two-gene differentiation process and a spatiotemporal organism model inspired by planaria.
title Incorporating stochastic gene expression, signaling-mediated intercellular interactions, and regulated cell proliferation in models of coordinated tissue development
topic Cell Behavior
Molecular Networks
Tissues and Organs
url https://arxiv.org/abs/2501.11271