Somatic reprogramming has relied heavily on theoretical models that view differentiation in terms of developmental branch point decisions. Recent studies in Cell now reveal a dominant role of the microenvironment in shaping epigenetic identity of macrophages, thus providing support for alternative models of cell fate acquisition.
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Understanding cancer from a biophysical, developmental and systems biology perspective using the landscapes-attractor model.
Biosystems
January 2025
Ludwig Boltzmann Institute for Hematology & Oncology, Department of Medicine I, Comprehensive Cancer Center (CCC), Medical University of Vienna, Waehringer Guertel 18 - 20, A-1090, Vienna, Austria. Electronic address:
Biophysical, developmental and systems-biology considerations enable deeper understanding why cancer is life threatening despite intensive research. Here we use two metaphors. Both conceive the cell genome and the encoded molecular system as an interacting gene regulatory network (GRN).
View Article and Find Full Text PDFIntravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials.
JAMA
November 2023
Research Centre of the Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.
Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain.
Objective: To determine whether vitamin C improves outcomes for patients with COVID-19.
Design, Setting, And Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents.
Dynamical landscapes of cell fate decisions.
Interface Focus
August 2022
Mathematics Institute, University of Warwick, Coventry CV4 7AL, UK.
The generation of cellular diversity during development involves differentiating cells transitioning between discrete cell states. In the 1940s, the developmental biologist Conrad Waddington introduced a landscape metaphor to describe this process. The developmental path of a cell was pictured as a ball rolling through a terrain of branching valleys with cell fate decisions represented by the branch points at which the ball decides between one of two available valleys.
View Article and Find Full Text PDFStatistically derived geometrical landscapes capture principles of decision-making dynamics during cell fate transitions.
Cell Syst
January 2022
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:
Fate decisions in developing tissues involve cells transitioning between discrete cell states, each defined by distinct gene expression profiles. The Waddington landscape, in which the development of a cell is viewed as a ball rolling through a valley filled terrain, is an appealing way to describe differentiation. To construct and validate accurate landscapes, quantitative methods based on experimental data are necessary.
View Article and Find Full Text PDFGeometry of gene regulatory dynamics.
Proc Natl Acad Sci U S A
September 2021
Center for Studies in Physics and Biology, Rockefeller University, New York, NY 10065;
Embryonic development leads to the reproducible and ordered appearance of complexity from egg to adult. The successive differentiation of different cell types that elaborate this complexity results from the activity of gene networks and was likened by Waddington to a flow through a landscape in which valleys represent alternative fates. Geometric methods allow the formal representation of such landscapes and codify the types of behaviors that result from systems of differential equations.
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