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Ruscone2023 - Logical model of Tumor Cell Invasion

ABSTRACT: This model builds upon two published models focused on the early steps of metastasis by Cohen et al. and on EMT process by Selvaggio et. al. The initial model of Cohen and colleagues was built with two inputs: the ECMenv, which monitored the status of the extracellular matrix, and DNA_damage, which considered DNA alterations that trigger death signals. Four additional inputs were added to account for the presence of Oxygen, growth factors (as GF), TGFbeta and the contact with other neighboring cells (as Neigh). The phenotypes, or outputs of the model include CellCycleArrest, Apoptosis, EMT, ECM_adh (for cell adhesion), ECM_degrad (for cell degradation), Cell_growth (for the dynamics of the tumor growth) and Cell_freeze (for cell motility ability). New genes and pathways include mechanisms around p63 and SRC. Genes from the Hippo pathway and RhoGTPases, such as YAP1, FAK and RAC1 were also inserted to link external signals (i.e., cell–cell contact, stiffness of the extracellular matrix, and stress signals) and intracellular regulation. The resulting network encompasses 45 nodes, with 6 input nodes, representing the possible interactions of an individual cell with external elements, and 8 output nodes or read-outs describing the possible observed phenotypes. This model was initially developed as a MaBoSS model for a multi-scale model of tumor invasion, developed with PhysiBoSS. As SBML-qual cannot describe fully a MaBoSS model yet, we also include the MaBoSS BND and CFG files.

SUBMITTER: Noël V

PROVIDER: MODEL2304070002 | BioModels | 2023-06-27

REPOSITORIES: BioModels

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Project description:We sought to characterize cellular heterogeneity in the human cerebral cortex at a molecular level during cortical neurogenesis. We captured single cells and generated sequencing libraries using the C1TM Single-Cell Auto Prep System (Fluidigm), the SMARTer Ultra Low RNA Kit (Clontech), and the Nextera XT DNA Sample Preparation Kit (Illumina). We performed unbiased clustering of the single cells and further examined transcriptional variation among cell groups interpreted as radial glia. Within this population, the major sources of variation related to cell cycle progression and the stem cell niche from which radial glia were captured. We found that outer subventricular zone radial glia (oRG cells) preferentially express genes related to extracellular matrix formation, migration, and stemness, including TNC, PTPRZ1, FAM107A, HOPX, and LIFR and related this transcriptional state to the position, morphology, and cell behaviors previously used to classify the cell type. Our results suggest that oRG cells maintain the subventricular niche through local production of growth factors, potentiation of growth factor signals by extracellular matrix proteins, and activation of self-renewal pathways, thereby contributing to the developmental and evolutionary expansion of the human neocortex. For study version 2, we have updated this data set to include additional primary cells that we infer to represent microglia, endothelial cells, and immature astrocytes, as well as additional cells from the developing neural retina, and from iPS-cell derived cerebral organoids. The genes distinguishing these cell populations may reveal biological processes supporting the diverse functions of these cell types as well as vulnerabilities of specific cell types in human genetic diseases and in viral infections. For study version 3, we have updated the data set to include additional primary cells, including those published in Nowakowski, et al., Science 2017: "Spatiotemporal Gene Expression Trajectories Reveal Developmental Hierarchies of the Human Cortex" (in press)

Project description:Background: Although quiescence—reversible cell-cycle arrest—is a key part in the life history and fate of many mammalian cell types, the mechanisms of gene regulation in quiescent cells are poorly understood. We sought to clarify the role of microRNAs as regulators of the cellular functions of quiescent human fibroblasts. Results: Using microarrays, we discovered that the expression of the majority of profiled microRNAs differed between proliferating and quiescent fibroblasts. Fibroblasts induced into quiescence by contact inhibition or serum starvation had similar microRNA profiles, indicating common changes induced by distinct quiescence signals. By analyzing the gene expression patterns of microRNA target genes with quiescence, we discovered a strong regulatory function for miR-29, which is downregulated with quiescence. Using microarrays and immunoblotting, we confirmed that miR-29 targets genes encoding collagen and other extracellular matrix proteins and that those target genes are induced in quiescence. In addition, overexpression of miR-29 resulted in more rapid cell cycle re-entry from quiescence. We also found that let-7 and miR-125 were upregulated in quiescent cells. Overexpression of either one alone resulted in slower cell cycle re-entry from quiescence, while the combination of both together slowed cell cycle re-entry even further. Conclusions: microRNAs regulate key aspects of fibroblast quiescence including the proliferative state of the cells as well as their gene expression profiles, in particular, the induction of extracellular matrix proteins in quiescent fibroblasts. microRNAs in human neonatal dermal fibroblasts in 3 cell cycle conditions (proliferating, 4 days serum starved, 7 days contact inhibited) were analyzed by one color microarray. 3 separate fibroblast cell lines from different human donors were analyzed for each condition, with two separate labeling and hybridization samples for each cell line. In total, 18 samples were hybridized to the microRNA microarray.

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Ruscone2023 - Logical model of Tumor Cell Invasion

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