CM – Developmental model shows forms of cell lines and connections for regeneration


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June 7, 2021

from the Institute for Basic Sciences

Various forms of complex multicellular organisms have evolved on Earth, from simple Volvox carterii with only two cell types to humans with more than 200 cell types. All of them descend from a single zygote and their developmental processes depend on a switch-like gene regulation. These processes have been studied in detail in a number of model organisms such as the C. elegans worm and the D. melanogaster fruit fly. It is also known that the key molecules and mechanisms involved in the development of multicellular organisms are highly conserved across species.

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It is also noteworthy that only a handful of molecules and mechanisms that go into the development of a multicellular organism can produce such a wide variety of shapes and complexity. How this is possible with a simple mathematical model was recently investigated by researchers from the Center for Soft and Living Matter of the Institute for Basic Science. With this work they tried to answer two seemingly contradicting questions: What are the limits of the diversity that can be created by development, and what common characteristics do all multicellular organisms have during their development.

Three processes are biological development common in all multicellular organisms: cell division, cellular signal transmission and gene regulation. As such, the model of this study generated millions of these rules and examined them in an unbiased manner. The maps generated by the model show how one cell type changes into another during the life of the organism. Earlier cell type maps based on single cell transcriptomics are traditionally tree-like, with stem cells sitting at the root of the tree and increasingly specialized cells appearing downstream along the branches of the tree. However, the cell type maps created with the new mathematical model were anything but tree-like; It was found that there were many cross-links between different branches of the cell types. These led to directed acyclic graphs, and tree lines were found to be the least common. This means that in the maps generated by the model, several development routes can converge on the terminal cell type.

Surprisingly, it was also found that many organisms generated by the mathematical model were equipped with the ability to regenerate lost cells without the authors imposing a selection. If a single cell type is isolated from the adult organism, a single cell could transform into and replenish all other cell types. This ability to create all cells in the body is called pluripotency, and it is these cells that gave the organisms in the model the ability to regenerate whole bodies. Interestingly, most tree-type lines contained fewer pluripotent cells compared to other chart types.

While mammals, including humans, are particularly poor at regenerating damaged parts, many animals such as worms and hydra are exceptionally good at this ability. Indeed, full body regeneration is widespread in the multicellular animal tree of life, and it has therefore been hypothesized that full body regeneration may be an epiphenomenon of biological development itself. The fact that pluripotency appeared in this very simplified model suggests that this property is likely due to the development process itself and does not require any special additional components to implement it.

In addition to these results, the The framework of this model can be used to study many more aspects of development. This generative model is simple and modular and can easily be extended to investigate important processes that were not considered in the present study, such as the effect of the spatial arrangement of cells and the effect of cell death. The researchers also described some possible real-world experiments to test some of the predictions of their mathematical model. It is hoped that the framework of this model will prove useful in uncovering new developmental features that can have a wide range of implications in developmental biology and regenerative medicine.

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A simple model of development shows shapes of cell lines and connections for regeneration on
Development model shows shapes of cell lines and links to regeneration


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