A Stem Cell Zoo Reveals Surprising Differences in Embryogenesis | TS Digest


Human embryos take much longer to develop than mouse embryos.1 Scientists thought that this was because humans are larger, but a new study has overturned that idea.2 Researchers from the European Molecular Biology Laboratory found that species-specific gene expression likely regulates biochemical reaction speeds and consequently the developmental tempo.

The team first secured stem cells from rhinoceroses to test an animal bigger than humans. Because gestation includes both embryogenesis and a phase of fetal growth, the researchers had no clue if rhinos’ long gestation reflected their embryonic development speed. As the stem cells differentiated in vitro, the researchers followed the developmental pace through the expression of the segmentation clock, a set of genes that creates segments in the embryo from which the vertebrae, ribs, and skeletal muscles eventually form. The genes are expressed in waves, where each wave crest creates a segment. 

They saw that rhino development was faster than that of humans. “That was very shocking,” said coauthor developmental biologist Jorge Lázaro. “We thought it was going to be super slow.” Testing rabbits, cattle, and marmosets confirmed that development pace didn’t correlate with body weight.

     This is an image of a bioluminescent from gene expression reporter in stem cells from a rhinoceros.

Jorge Lázaro and his team measured the oscillation of the segmentation clock through a bioluminescent reporter, shown in this image of induced pluripotent stem cells from a rhinoceros.

European Molecular Biology Laboratory

Instead, the researchers found that the faster the segmentation clock ticked, the quicker reaction rates were for key embryogenesis proteins. The expression of thousands of genes involved in biochemical processes such as nuclear transport and RNA processing also correlated with segmentation clock speed. This corroborated the team’s earlier findings in mice and humans.1 Consequently, they proposed that species-specific transcriptomic profiles control biochemical reaction speeds and ultimately developmental pace.

“The lengths they’ve gone to to analyze this evolutionary question is really beyond what anyone’s done before,” said developmental biologist Andrew Oates from École Polytechnique Fédérale de Lausanne, who was not involved in the study. However, to him, pinning the mechanism on “genes related to biochemical reactions” is too vague. “It’s still rather mysterious. [Although] probably the answer is in that set of genes.”

Lázaro might soon provide clarity. He plans to tweak the gene expression and speed up development in the stem cells. That should elucidate the mechanism and yield a blueprint for accelerating development elsewhere, for instance in organoids, some of which can take months to mature.

References

  1. Matsuda M, et al. Science. 2020;369(6510):1450-1455.
  2. Lázaro J, et al. Cell Stem Cell. 2023;30(7):938-949

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