2 research outputs found
Modelling the role of polarity and geometry in cell-fate dynamics of mammary organoids
Mammary organoids are three-dimensional structures that are derived from
mammary gland cells and can recapitulate the complex architecture and
functionality of the mammary gland in vitro. Mammary organoids hold great
promise for advancing our understanding of mammary gland biology, breast
cancer, and precision medicine. However, phenotypic and genetic instabilities
observed in long-term expansion limit their applications to prolonged experiments
and large-scale production.
A proposed factor driving this organoid-wise heterogeneity is plasticity
within mammary epithelial cells, the phenotypic switching of cells. Therefore,
we examine the dynamics of key intracellular pathways that govern cell-fate
commitment in mammary organoids. Specifically, we explore the influence of
local tissue geometry and polarity in cell-cell signalling in stabilising cell-fate
determinants using a combination of analytic and numerical multiscale modelling
approaches.
We introduce interconnected dynamical systems, graph-coupled dynamical
systems with input-output representations to describe intercellular signal flow
between cells. Exploiting structural properties of the bilayer graphs describing
mammary tissue architecture, we derive low-dimensional forms of these models
enabling the analytic examination of the interplay of structure and polarity on
cell-fate patterning, extending existing methods to include pathway crosstalk and
providing rigorous links between low-dimensional and their associated large-scale
representations.
Supporting the analytic investigations of static spatial domains with cellbased
modelling, we provide evidence that sufficiently strong cell-cell signal
polarity has the capacity to generate and sustain bilayer laminar patterns of
Notch1, a critical cell-fate determinant and inducer of plasticity in mammary
epithelial cells. Furthermore, we demonstrate how local tissue curvature can
relax the constraints of polarity supporting healthy tissue growth and supporting
branching morphologies. Fundamentally, this study highlights the significance of
cell signalling polarity as a control mechanism of cell-fate commitment. Thus,
the establishment and maintenance of epithelial polarity should be considered in
long-term mammary organoid expansion protocol development
Spacelab Science Results Study
Beginning with OSTA-1 in November 1981 and ending with Neurolab in March 1998, a total of 36 Shuttle missions carried various Spacelab components such as the Spacelab module, pallet, instrument pointing system, or mission peculiar experiment support structure. The experiments carried out during these flights included astrophysics, solar physics, plasma physics, atmospheric science, Earth observations, and a wide range of microgravity experiments in life sciences, biotechnology, materials science, and fluid physics which includes combustion and critical point phenomena. In all, some 764 experiments were conducted by investigators from the U.S., Europe, and Japan. The purpose of this Spacelab Science Results Study is to document the contributions made in each of the major research areas by giving a brief synopsis of the more significant experiments and an extensive list of the publications that were produced. We have also endeavored to show how these results impacted the existing body of knowledge, where they have spawned new fields, and if appropriate, where the knowledge they produced has been applied