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Human and mouse cells run at different speeds

A new study shows that differences between species in the rate of development are based on the speed of their biochemical reactions. The work has been led by Miki Ebisuya at EMBL Barcelona and RIKEN BDR and has had the participation of Jordi Garcia-Ojalvo at UPF.


Scientists from the RIKEN Center for Biosystems Dynamics Research, EMBL Barcelona, Universitat Pompeu Fabra, and Kyoto University have found that the rhythmic signal of the segmentation clock – a genetic network that governs the sequential formation of the body pattern in embryos – beats more slowly in humans than in mice. The difference is due to certain biochemical reactions progressing in human cells at a lower rate.

Each species with its own tempo

In the early phase of vertebrate development, the embryo develops into a series of segments that eventually differentiate into various types of tissues, such as muscles or bones. This process is governed by an oscillating biochemical process, known as the segmentation clock, which varies in speed between species. In mice, each oscillation of the segmentation clock takes about two hours, while in human cells it takes five hours. However, why the length of this cycle varies between species has remained a mystery.

To solve this enigma, the researchers used mouse embryonic stem cells and human induced pluripotent stem (iPS) cells – both of which have the ability to specialise to form other cell types in the body. The researchers transformed them into a cell type known as presomitic mesoderm (PSM), whose development is governed by the segmentation clock.

The scientists first examined whether the difference in oscillation frequency between the two cell types was due to the ways that multiple cells communicate with each other, or instead could be found in the biochemical processes within each individual cell. Using experiments that either isolated cells or blocked important signals, they found out that it was the biochemical processes within individual cells that were responsible.

Different biochemical reaction speeds explain why mice develop faster than humans

Once it was clear that the key processes governing segmentation clock oscillations occurred inside the cells, the researchers suspected that the difference might be due to a master gene called HES7. They performed a number of experiments in which they swapped the HES7 genes between human cells and mouse cells, but to their surprise this did not affect the cycle.

“Failing to show a difference in the gene expression left us with the possibility that the difference in oscillation frequency was driven by different biochemical reactions within the cells,” says corresponding author Miki Ebisuya, Group Leader at EMBL Barcelona, who performed the work at RIKEN BDR and at EMBL.

But what exactly were these differences? To find out, the team looked at the degradation rate of the HES7 protein, which plays a key role in the oscillation cycle in both mice and humans. They observed that both the human and the mouse version of the HES7 protein were degraded more slowly in human cells than in mouse cells. They also discovered that the time it took cells to transcribe the HES7 gene into messenger RNA (mRNA), to process the mRNA molecule, and to translate it into proteins was significantly different. “We could thus show that it was indeed the cellular environment in human and mouse cells that made the difference in the biochemical reaction speeds, and thus in the time scales involved,” says Ebisuya.

Towards a better understanding of vertebrate development

As Ebisuya explains, their observations led the scientists to develop the concept of ‘developmental allochrony’, a term that means something develops over different times. “Our study will help us to understand the complicated process through which vertebrates develop,” says Ebisuya. “One of the key remaining questions we’d like to answer is what exactly drives the differences in reaction rates in mouse and human cells. We plan to shed light on this mystery in the near future.”   

Reference article:

Matsuda, M et al. Science, published online 18 September 2020. DOI: 10.1126/science.aba7668


Profiles of the protagonists:

Jordi Garcia-Ojalvo


SDG - Sustainable Development Goals:

Els ODS a la UPF


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