Gene-free landscape models for development
Fate decisions in developing tissues involve cells transitioning between a set of discrete cell states. Geometric models, often referred to as Waddington landscapes, are an appealing way to describe differentiation dynamics and developmental decisions. We consider the differentiation of neural and mesodermal cells from pluripotent mouse embryonic stem cells exposed to different combinations and durations of signalling factors. We developed a principled statistical approach using flow cytometry data to quantify differentiating cell states. Then, using a framework based on Catastrophe Theory and approximate Bayesian computation, we constructed the corresponding dynamical landscape. The result was a quantitative model that accurately predicted the proportions of neural and mesodermal cells differentiating in response to specific signalling regimes. Taken together, the approach we describe is broadly applicable for the quantitative analysis of differentiation dynamics and for determining the logic of developmental cell fate decisions.
Exploring mechanisms of human brain expansion in cerebral organoids
The human brain sets us apart as a species, with its size being one of its most striking features. Brain size is largely determined during development as vast numbers of neurons and supportive glia are generated. In an effort to better understand the events that determine the human brain’s cellular makeup, and its size, we use a human model system in a dish, called cerebral organoids. These 3D tissues are generated from pluripotent stem cells through neural differentiation and a supportive 3D microenvironment to generate organoids with the same tissue architecture as the early human fetal brain. Such organoids are allowing us to tackle questions previously impossible with more traditional approaches. Indeed, our recent findings provide insight into regulation of brain size and neuron number across ape species, identifying key stages of early neural stem cell expansion that set up a larger starting cell number to enable the production of increased numbers of neurons. We are also investigating the role of extrinsic regulators in determining numbers and types of neurons produced in the human cerebral cortex. Overall, our findings are pointing to key, human-specific aspects of brain development and function, that have important implications for neurological disease.
2nd In-Vitro 2D & 3D Neuronal Networks Summit
The event is open to everyone interested in Neuroscience, Cell Biology, Drug Discovery, Disease Modeling, and Bio/Neuroengineering! This meeting is a platform bringing scientists from all over the world together and fostering scientific exchange and collaboration.
2nd In-Vitro 2D & 3D Neuronal Networks Summit
The event is open to everyone interested in Neuroscience, Cell Biology, Drug Discovery, Disease Modeling, and Bio/Neuroengineering! This meeting is a platform bringing scientists from all over the world together and fostering scientific exchange and collaboration.
Retinal organoids from pluripotent stem cells: from development to disease
Functional characterization of human iPSC-derived neurons at single-cell resolution
Recent developments in induced pluripotent stem cell (iPSC) technology have enabled easier access to human cells in vitro. With increasing availability of human iPSC-derived neurons, both healthy and disease cell lines, screening compounds for neurodegenerative diseases on human cells can potentially be performed in the earlier stages of drug discovery. To accelerate the functional characterization of iPSC-derived neurons and the effect of compounds, reproducible and relevant results are necessary. In this webinar, the speakers will: Introduce high-resolution functional imaging of human iPSC-derived neurons Showcase how to extract functional features of hundreds of cells in a cell culture sample label-free Discuss electrophysiological parameters for characterizing the differences among several human neuronal cell lines