Scientists found stem cell network in ancient fish

A 'living fossil' is the key to understanding stem cells.

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The support of pluripotent cells over time is an essential feature of development. Pluripotent cells are stem cells that can develop into all other cells. Understanding the development of pluripotent stem cells into a heart can help replicate this process in laboratory.

An ancient fish called a ‘living fossil’ has helped scientists understand the basics of stem cells. Scientists at the University of Copenhagen have discovered that the coelacanth fish contains the master gene that regulates stem cells and maintains pluripotency. This gene, known as OCT4 in humans and mice, was found to be replaceable with a coelacanth variant in mouse stem cells.

The coelacanth has been referred to as a “living fossil” and is classified separately from mammals due to the fact that it evolved into its current form about 400 million years ago. It mimics the first animals to transition from the sea to land because it possesses fins resembling limbs.

Assistant Professor Molly Lowndes said, “By studying its cells, you can go back in evolution, so to speak.”

OCT4-protein
3D-model of the OCT4-protein. Illustration: Woranop Sukparangsi.

Assistant Professor Woranop Sukparangsi continues: “The central factor controlling the gene network in stem cells is found in the coelacanth. This shows that the network existed early in evolution, potentially as far back as 400 million years ago.”

Ph.D. student Elena Morganti said, “The beauty of moving back in evolution is that the organisms become simpler. For example, they have only one copy of some essential genes instead of many versions. That way, you can separate what is important for stem cells and use that to improve how you grow stem cells in a dish.”

Scientists discovered that the stem cell network is far older than previously believed and can be found in extinct species. They also discovered how evolution changed the gene network to enable pluripotent stem cells.

stem cell genes from over 40 animals
Scientists looked at the stem cell genes from over 40 animals. For example sharks, mice and kangaroos. Illustration: Woranop Sukparangsi.

Over 40 animal stem cell genes were examined: kangaroos, mice, and sharks. The animals were chosen to represent a good cross-section of the major evolutionary turning points.

The study employed artificial intelligence to create three-dimensional models of the various OCT4 proteins. The protein’s overall structure has been preserved throughout evolution, according to the experts. While the parts of these proteins known to be crucial for stem cells do not change, species-specific variations in these proteins that appear unrelated to one another change their orientation, which may impact how well they maintain pluripotency.

Joshua Mark Brickman said“This a fascinating finding about evolution that would not have been possible before the advent of new technologies. You can see it as evolution cleverly thinking, we do not tinker with the ‘engine in the car,’ but we can move the engine around and improve the drive train to see if it makes the car go faster.”

Journal Reference:

  1. Sukparangsi, W., Morganti, E., Lowndes, M. et al. Evolutionary origin of vertebrate OCT4/POU5 functions in supporting pluripotency. Nat Commun 13, 5537 (2022). DOI: 10.1038/s41467-022-32481-z