Modeling how cells choose their fates

The Elowitz lab is at Caltech.

It may seem hard to believe, but each of us began as a single cell that grew into trillions of other cells. Each of our cells has a different function, for example, immune cells learn to fight off disease, skin cells protect us from the outside world, and muscle cells enable movement.

All of these cell types are derived from pluripotent stem cells. Stem cells are like a blank slate that can become any type of cell. Think of how a child grows into an adult and chooses a career and life path. Stem cells choose their careers based on complicated chains of reactions within a cell's genome.

Caltech's Michael Elowitz, professor of biology and bioengineering and Howard Hughes Medical Institute Investigator, and his team have developed a synthetic genetic circuit that demonstrates how cells choose their fates. There is a paper about the research in the journal Science.

The researchers showed how a relatively small set of components and interactions are sufficient to establish and control a larger number of cellular states through a property called "multistability." MultiFate allows researchers to engineer a single living cell that can change into different states that are stable on their own but are capable of performing a distinct function, similar to what happens in our own bodies.

Each of the 7 cell states of the MultiFate circuit can make the cell glow in different colors. There are many cells that are genetically identical and growing in the same environment, but not in the same MultiFate state. MultiFate ensures that cells remember their fate as they grow and divide, causing all cells in a colony to maintain the same color. The Elowitz lab is at Caltech.

The artificial circuit of genes was designed to function in cells grown in the lab without disrupting normal cellular processes. The MultiFate circuit consists of three genes, each coding for a corresponding transcription factor that is labeled with a red, green, or blue color. Each of the three proteins binding to its own DNA turns on. The three types of proteins can block each other's activity.

This type of circuit can allow a cell to exist in as many as seven different states. Each of these states expresses a different combination of the red, green, and blue proteins, making the cells glow in any of seven different colors: red, green, blue, cyan, white, and yellow. The cell stays in one of the states if it is perturbed by the researchers. The cells are locked into their fates, so a cell can pass its color to its daughter cells as it grows.

The researchers designed MultiFate so that they could induce the cell to switch between seven states using certain drugs.

The work shows how designing and building synthetic circuits from scratch can provide insights into fundamental biological phenomena. MultiFate is designed from the bottom up. Elowitz says that it helps explain how cells can exist in so many fates and that it could provide a foundation for extending cell therapies to perform more complex therapeutic functions that no single cell type could provide.

The paper is about synthetic multistability. The paper's first author is Zhu. The Caltech graduate student and the Universitat Pompeu Fabra student are co-authors.

Science has more information about Synthetic multistability in mammalian cells. There is a science.abg9765.

Science journal information.

The model of how cells choose their fates was retrieved from thephys.org.

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