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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…

Molecular Networks · Quantitative Biology 2014-09-11 Alex H. Lang , Hu Li , James J. Collins , Pankaj Mehta

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…

Quantitative Methods · Quantitative Biology 2023-09-15 Rongsheng Huang , Qiaojun Situ , Jinzhi Lei

An adult human body is made up of some 30 to 40 trillion cells, all of which stem from a single fertilized egg cell. The process by which the right cells appear to arrive in their right numbers at the right time at the right place --…

Subcellular Processes · Quantitative Biology 2024-12-20 Sean T. Vittadello , Léo Diaz , Yujing Liu , Adriana Zanca , Michael P. H. Stumpf

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…

Molecular Networks · Quantitative Biology 2020-05-06 Yuuki Matsushita , Kunihiko Kaneko

The baseline level of transcription, which is variable and difficult to quantify, seriously complicates the normalization of comparative transcriptomic data, but its biological importance remains unappreciated. We show that this currently…

Molecular Networks · Quantitative Biology 2022-07-26 Gilles Flouriot , Charly Jehanno , Yann Le Page , Pascale Le Goff , Benjamin Boutin , Denis Michel

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.…

Molecular Networks · Quantitative Biology 2026-04-15 Sascha H. Hauck , Sandip Saha , Narsis A. Kiani , Jesper N. Tegner

Cells use genetic switches to shift between alternate stable gene expression states, e.g., to adapt to new environments or to follow a developmental pathway. Conceptually, these stable phenotypes can be considered as attractive states on an…

Molecular Networks · Quantitative Biology 2021-06-18 Michael Assaf , Shay Be'er , Elijah Roberts

One of the most important problems in development is how epigenetic domains can be first established, and then maintained, within cells. To address this question, we propose a framework which couples 3D chromatin folding dynamics, to a…

Soft Condensed Matter · Physics 2016-10-25 Davide Michieletto , Enzo Orlandini , Davide Marenduzzo

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…

Cell Behavior · Quantitative Biology 2014-02-04 Motoki Nakagawa , Osamu Narikiyo

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…

Molecular Networks · Quantitative Biology 2015-05-18 Mille A. Micheelsen , Namiko Mitarai , Kim Sneppen , Ian. B. Dodd

Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of…

Molecular Networks · Quantitative Biology 2015-06-18 Daniel Jost

Embryonic development leads to the reproducible and ordered appearance of complexity from egg to adult. The successive differentiation of different cell types, that elaborates this complexity, result from the activity of gene networks and…

Quantitative Methods · Quantitative Biology 2022-05-11 David A. Rand , Archishman Raju , Meritxell Saez , Francis Corson , Eric D. Siggia

The spreading and regulation of epigenetic marks on chromosomes is crucial to establish and maintain cellular identity. Nonetheless, the dynamical mechanism leading to the establishment and maintenance of a given, cell-line specific,…

Soft Condensed Matter · Physics 2017-11-08 Davide Michieletto , Enzo Orlandini , Davide Marenduzzo

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…

Cell Behavior · Quantitative Biology 2026-05-12 Casey O. Barkan , Tom Chou

The epigenetic pathway of a cell as it differentiates from a stem cell state to a mature lineage-committed one has been historically understood in terms of Waddington's landscape, consisting of hills and valleys. The smooth top and…

Cell Behavior · Quantitative Biology 2013-06-12 Mithun K. Mitra , Paul R. Taylor , Chris J. Hutchison , T. C. B. McLeish , Buddhapriya Chakrabarti

The complexity of gene regulatory networks in multicellular organisms makes interpretable low-dimensional models highly desirable. An attractive geometric picture, attributed to Waddington, visualizes the differentiation of a cell into…

Biological Physics · Physics 2024-12-12 Gautam Reddy

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…

Molecular Networks · Quantitative Biology 2015-10-15 Jose Davila-Velderrain , Luis Juarez-Ramiro , Juan C. Martinez-Garcia , Elena R. Alvarez-Buylla

Networks in machine learning offer examples of complex high-dimensional dynamical systems reminiscent of biological systems. Here, we study the learning dynamics of Generalized Hopfield networks, which permit a visualization of internal…

Disordered Systems and Neural Networks · Physics 2023-12-07 Nacer Eddine Boukacem , Allen Leary , Robin Thériault , Felix Gottlieb , Madhav Mani , Paul François

In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the…

Epigenetics plays a key role in cellular differentiation and maintaining cell identity, enabling cells to regulate their genetic activity without altering the DNA sequence. Epigenetic regulation occurs within the context of hierarchically…

Quantitative Methods · Quantitative Biology 2024-09-11 Daria Stepanova , Meritxell Brunet Guasch , Helen M. Byrne , Tomás Alarcón
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