Each of the virtual tissues starts from one or more single cells. These cells grow and divide, producing daughter cells. Each and every cell in the simulation has its unique identity and unique internal state of molecule conentrations and active biological events, influenced by its internal signaling and gene regulatory network as well as signaling mechanisms with neighbouring cells and its environment.
Emerging behavior, replicating biology as closely as possible.
Development of Epidermal Tissue
This video shows development of epidermal tissue from a single basal stem cell, generating a population of skin cells (keratinocytes) that produce lipids (orange color). The self-organizing virtual tissue stabilizes as death of keratinocytes becomes balanced by replenishment from dividing basal stem cells.
Tumore Experiment of Epidermal Tissue
This video demonstrates the ability of the CellSim™ platform to alter very low level aspects of a virtual biological mechanism during its development.
Here we follow the development of a virtual epidermal tissue, as before, highlighting various markers starting with a basal, followed by keratin, lipid, comeocyte and then at step 500, an unaltered lineage marker. That is, an unaltered basal cell had its LineageUnaltered gene activated to show a normal flow of cells from a basal cell.
However, at step 1000, a basal cell had the suppression of its division removed and the LineageAltered gene activated to show flow of altered cells. By step 1300, the entire tissue was composed of descendants of the uninhibited cell.
Mammary Acinus Cell Development
Acini cells are the smallest functional unit of the breast. Several hundred acini cells in each breast produce milk into a separate duct funneled into the ductal system toward the nipple. Most breast cancers start in mammary acini, which are basic anatomical units of the mammary gland.
This video is a virtual mammary acinus phenotype throughout its development, starting from a single, virtual cell.
It starts with a cut plane showing only half of the cells, the inner cells differentiate then die off, leaving a hollow sphere which builds the extra cellular matrix.
Identical Acinus Cells in Different Environments
This video illustrates the effect of compression on mammary acinar development, where two cells with identical genomes but different physical environments grow side by side. The cell on the left is constrained to a narrow slice of space and the cell on the right is unconstrained.
This demonstrates that the resulting phenotype depends on the local conditions for each cell and for the entire tissue. Cells constrained to a plane lose contact with their neighbors and the tissue becomes fragmented. The mass of cells on the right grows normally, becomes hollow, and retains its shape for the remainder of development.
Shape homeostasis in living tissues is an important but poorly understood phenomenon related to the general processes of allometric growth, tissue repair, regeneration, and cancer-related loss of normal controls on tissue size and morphology.
This video demonstrates CellSim‘s ability to highlight any of the various biological aspects of a “self organizing cluster” of virtual cells. Color coded descriptors depict separate properties such as lineage, cell growth, division, and cell death, primarily apoptosis, for pruning unwanted or inappropriately placed cells.
Macrophages are a type of white blood cell of the immune system that engulfs and digests anything that does not have, on its surface, proteins that are specific to healthy body cells, including cancer cells, microbes, cellular debris, foreign substances, etc.
This video demonstrates cell motility in a node signaling environment. The bacteria are emitting signals into the surrounding space and the large macrophage is moving in the direction of its subunit detecting the highest concentration of the bacterial signal. Once contact is made, the macrophage “eats” the bacterium by increasing adhesion to the extent that inner subunits pull the bacterium inside the macrophage.
In this video, a cell that is displaced from the acinus loses signalling from its neighbors and in response it consumes any internal resources not present in the original progenitor cell. This “reset function”, analogous to de-differentiation in vivo, returns the plucked cell to the same state as the cell which generated the original acinus.
A new acinus grows from this cell, and although the displaced cell is in the same state as the original starting cell, there are differences between the the original acinus and its regenerated.
Emulation of Stem Cell Niche
In the Drosophila testis, sperm must be replenished as required by a male’s reproductive effort. In these two videos, emulation of the testis niche was focused on production of a stable niche architecture from a single starting cell attached to extracellular matrix (ECM). The top video shows the hub cell anchorage to ECM, while the bottom video shows the germ line stem cells (GSC). When a GSC divides, two daughter cells result: one is a stem cell that replenishes the stem cell population of the niche, and the other that divides and differentiates to yield 16 sperm, following four rounds of cell division.