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STEM CELL DIFFERENTIATION: FROM PLANTS TO HUMANS

Sapienza University has coordinated the first study to analyse the biological mechanism used by the plants to implement the differentiation of stem cells and adapt to the environment. The study, which has been published on the Proceedings of the National Academy of Sciences, is a methodological innovation in observing cellular processes and could be extended to human stem cells.

The research group coordinated by Sabrina Sabatini started by studying the regenerative mechanisms of plants, which are capable of continuously producing new "organs" such as roots, leaves and flowers, but which are also particularly useful for collecting invaluable information also on human physiology. During a series of 4-year experiments, the research group identified the molecular mechanism that activate the process whereby plant stem cells are transformed into specialized cells.

The group developed a mathematical model of the root that faithfully reproduces the behaviour of this "organ" through computer simulations. This allowed them to obtain precise predictions of root development, with the variation of certain genetic and physiological parameters, that would have been endless, if not impossible, to obtain with laboratory experiments.

In particular, the scientists focused on auxin, a substance that, by governing tissue development, is able to stimulate plant growth and is therefore referred to as a morphogen. The important role of auxin in cell division has already been detected, but the distribution and minimum concentration of auxin needed to induce cell differentiation remained unknown.

Now, the new model developed by Sabatini and colleagues has shed light on this point. The group discovered the molecular mechanism though which the distribution of auxin concentration determines the point where stem cells differentiate by specialising instead of replicating through division. The root is thus able to change its dimensions to adapt to the different needs imposed by the environment. The discovery was then confirmed by in vivo experiments.

One of the first mathematical models developed In Bio-Medicine focused on the heart. In 1928, Dutch Physicist Balthasar van der Pol produced a heartbeat with an artificial electrocardiogram that allowed him to reproduce and study some disorders. "We did a similar operation to analyse the plants," explained Prof. Sabatini, "but with a higher level of precision. In fact, our model faithfully reproduces the structure of a root, taking into account its geometry and that of each cell composing it."

Just as in plants, humans also have a morphogen essential to growth: retinoic acid. Auxin can be considered the plant equivalent of retinoic acid. And similar patterns may help us to understand how the distribution of these substances controls the growth and operation of ssecific organ.

"We have still not been verified whether there is a minimum morphogenic threshold for human cells, as we did for plant cells. Studying this aspect could help us better understand how the differentiation of human stem cells works," points out Prof. Sabatini. That is why the biological mechanism, described in the article published on Proceedings of the National Academy of Sciences (PNAS), could also be helpful to understand the mechanisms that regulate the activity of human stem cells.

References:

Auxin Minimum Triggers the Developmental Switch from Cell Division to Cell Differentiation in the Arabidopsis Root. Di Mambro R, De Ruvo M, Pacifiers E, Salvi E, Sozzani R, Benfey PN, Busch W, Novak O, Ljung K, Di Paola L., Marée AFM, Constantine P, Grieneisen VA, Sabatini S. Proceedings of the National Academy of Sciences 2017 Sep 5. Doi: 10.1073/pnas.1705833114.