Welcome to the latest human-mouse chimeras

human mouse chimera

A chimera was a mythological animal in the Antique Greece, but now a biological chimera is an animal with cells from different organisms. In recently published research in Science Advances 1, researchers show the result of the newest trial to introduce human cells into a mouse embryo. The last human mouse chimera.

This was not the first time that scientists have tried to grow human cells in other animals, but it seems that is all not that easy. That is why the results of this study are so striking because in some of the mouse embryos where the researchers implanted early stem cells, up to 4% of all embryonic cells were human.

The trick to the success of this trial was to reset the human stem cells to be even more totipotent than ever, so that they could match the clocks of the mouse embryonic cells. To do so, the researchers inhibited mTOR, a protein implicated in a very important signalling cascade related to cell differentiation, for three hours before injecting batches of 8-10 human reset stem cells into 60-80 cell mouse embryos, which were then left to develop for 17 days.

The resulting embryos developed tissue-like structures, in some of which, DNA analysis showed human cell contribution. For instance, some of those early human stem cells developed to form part of the liver, heart, bone marrow and blood. They were even found in tissues which would eventually form the brain or eye photoreceptors.

An interesting fact about the developmental characteristics of this human mouse chimera is that the speed of differentiation of human stem cells is accelerated when in the mouse to match up to the developmental speed of their host.

Finally, if you are wondering why would we need chimeras at all, the reasons are varied: on the one hand, chimeras could allow us to understand the embryonic development of human stem cells, or could help to create compatible transplants without the need for clones, or…

But this is still science fiction. For now, we are left with a tiny embryonic chimera, much like that of the Greeks.

References

  1. Zhixing Hu et al (2020) Transient inhibition of mTOR in human pluripotent stem cells enables robust formation of mouse-human chimeric embryos Science Advances doi: 10.1126/sciadv.aaz0298

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