Computational Model of Microglial Cell Dynamics During Morphogenesis of Brain Microvasculature

Biologically inspired multicellular systems models that are fully computable (e.g., a virtual embryo) can be used to titrate critical phenomena during tissue development, homeostasis, and disease; however, in silico reconstitution of a complex, self-organizing morphogenetic system from unidimensional data (embryogeny) remains a challenge. Microglial cells are essential building blocks of microvascular development (angiogenesis) and permeability (barriergenesis), and are often altered in neurodevelopmental disorders (e.g., RTT, FAS, ASD). To begin to unravel their complex roles in fetal brain homeostasis, a small working prototype of perineural vascular development was constructed in CompuCell3D.org to translate microglial function into consequences on emergent microvascular patterning. Our vision is to execute the models for predictive biology of neurodevelopmental disorders, including chemical exposures during pregnancy. DISCLAIMER: Does not necessarily reflect Agency policy. Computational Model of Cell Fate Specification in a 3D Synthetic Gastruloid Simulator Kaitlyn Barham US EPA, Center for Computational Toxicology and Exposure The embryonic body plan is ‘decoded’ during gastrulation, the hallmark of which is primitive streak formation in the epiblast. Using CompuCell3D, we modeled the human epiblast evolving a primitive streak through epithelial-mesenchymal transition of pluripotent stem cells and self-organizing endo-mesodermal progenitors through a network of morphogenetic signals (e.g., FGF, WNT, NODAL). Executing the simulation drives a synthetic HOX clock that patterns the emergence mesodermal cell fates (chordamesoderm, paraxial, lateral plate, extraembryonic). Synthetic perturbations introduced into the model simulate quantitative genetic and/or environmental influences on positional information to essentially ‘recode’ the mesodermal topography. This small working prototype model translates global or local perturbations to the system into mesodermal fate based on spatio-temporal colinearity of a synthetic HOX clock. DISCLAIMER: Does not necessarily reflect Agency policy Moderator: James A. Glazier, PhD, Indiana University, Bloomington To learn more see: Thomas, Russell S., Tina Bahadori, Timothy J. Buckley, John Cowden, Chad Deisenroth, Kathie L. Dionisio, Jeffrey B. Frithsen et al. "The next generation blueprint of computational toxicology at the US Environmental Protection Agency." Toxicological Sciences 169, no. 2 (2019): 317-332. https://pubmed.ncbi.nlm.nih.gov/30835285/ To view the slides for this video visit: https://drive.google.com/file/d/1etnI_NNWj_orjc318H7DkSaIbhcBX0w_/ and https://drive.google.com/file/d/1YaNwIFfse2THgJb6FR_3Q1Sf0X9ayzw4/ If you found this video useful, please check out our other videos on computational modeling, infection and immunology: https://tinyurl.com/GLIMPRINTVideos Please consider joining our IMAG/MSM WG on Multiscale Modeling and Viral Pandemics: https://www.imagwiki.nibib.nih.gov/content/msm-viral-pandemics-meetings Please also consider joining the Global Alliance for Immune Prediction and Intervention: http://glimprint.org/