Contributors
Lorenzo Veschini, King's College London. Title: “High content image analysis and multiscale cell simulations to investigate emerging cellular heterogeneity in endothelia”
Institution/ Affiliation
Lorenzo Veschini, King's College London.
Presentation Details (date, conference, etc.)
November 11, 2021, IMAG/MSM WG on Multiscale Modeling and Viral Pandemics
- Lorenzo Veschini, King's College London. Title: “High content image analysis and multiscale cell simulations to investigate emerging cellular heterogeneity in endothelia” Abstract: Understanding healthy and pathological tissue development and functions requires measuring cell molecular signalling, movements, and interactions. Gold standard single cells NGS allows evaluating cell transcriptome and metabolism with great depth and have highlighted the extent of cell heterogeneity within tissues. However, current NGS technologies fail to capture spatial relationships and dynamic phenotypic changes in cells within tissues. Image analysis techniques powered by machine learning allows capturing spatial relationships among cells and evaluating cellular crosstalk. Imaging data are also translatable to multiscale in silico tissue simulations to estimate dynamics of cell movements and molecular crosstalk. We have developed an open-source platform, the endothelial cells profiling tool (EC-PT), to measure individual EC phenotype within endothelia. ECPT includes tools to measure spatial autocorrelation of features such as NOTCH signalling at single cell level allowing to estimate dynamic molecular crosstalk between neighbouring EC and across the whole endothelium. ECPT seamlessly integrates with the multiscale cellular simulation environment Compucell3D. We will present data demonstrating previously unappreciated degrees of EC heterogeneity within the same EC monolayer suggesting a high degree of plasticity. Furthermore, we have developed simulations of NOTCH signalling in cell monolayers using Compucell3D and suggesting that such heterogeneity can result from dynamic and relatively fast phenotypic adjustments at the single cell level. These results provide possible molecular explanations of how EC within the same vascular bed can exert different functions such as proliferation (self-renewal), maintenance of endothelial barrier as well as differential responses to drugs and potentially to pathogens. YouTube and Slides.