Searching old stem cells that stay young forever

The sea anemone Nematostella vectensis is potentially immortal. Using molecular genetic methods, developmental biologists led by Ulrich Technau from the University of Vienna have now identified possible candidates for multipotent stem cells in the sea anemone for the first time. These stem cells are regulated by evolutionary highly conserved genes, which in humans are usually only active in the formation of egg and sperm cells, but give ancient animal phyla such as cnidarians a high degree of regenerative capacity to even escape ageing. The results are currently being published in Science Advances and could also provide insights into the human ageing process in the future.

"We live as long as our stem cells" is a somewhat bold but essentially accurate statement.

Stem cells contribute to the constant renewal of various cells and tissues in humans, e.g. blood cells, skin or hair.

If stem cells lose this ability or their number decreases in the course of life, the body ages or develops diseases.

Stem cells are therefore of great interest for biomedical research.

While humans and most vertebrates can only regenerate parts of certain organs or limbs, other animal groups have far stronger regeneration mechanisms.

This ability is made possible by pluripotent or multipotent stem cells, which can form (differentiate) almost all cell types of the body.

The sea anemone Nematostella vectensis is also highly regenerative: it can reproduce asexually by budding and also shows no signs of ageing, which makes it an interesting subject for stem cell research.

However, researchers have not yet been able to identify any stem cells in these animals.

Using the new "Single Cell Genomics" method, Technau and his team could identify cells of a complex organism based on their specific transcriptome profiles and determine from which stem cells they have developed.

"By combining single-cell gene expression analyses and transgenesis, we have now been able to identify a large population of cells in the sea anemone that form differentiated cells such as nerve cells and glandular cells and are therefore candidates for multipotent stem cells," explains first author Andreas Denner from the University of Vienna.

They have remained undiscovered until now due to their tiny size.

These potential stem cells express the evolutionarily highly conserved genes nanos and piwi, which enable the development of germ cells (sperm and egg cells) in all animals, including humans.

By specifically mutating the nanos2 gene using the CRISPR gene scissors, the scientists were also able to prove that the gene is necessary for the formation of germ cells in sea anemones.

It has also been shown in other animals that this gene is essential for the production of gametes.

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Scientists investigate the evolution of animal developmental mechanisms, show how some of Earth's earliest animals evolved

Lacking bones, brains, and even a complete gut, the body plans of simple animals like sea anemones appear to have little in common with humans and their vertebrate kin. Nevertheless, new research from Investigator Matt Gibson, Ph.D., at the Stowers Institute for Medical Research shows that appearances can be deceiving, and that a common genetic toolkit can be deployed in different ways to drive embryological development to produce very different adult body plans.

It is well established that sea anemones, corals, and their jellyfish relatives shared a common ancestor with humans that plied the Earth's ancient oceans over 600 million years ago. A new study from the Gibson Lab, published in Current Biology on June 13, 2023, illuminates the genetic basis for body plan development in the starlet sea anemone, Nematostella vectensis. This new knowledge paints a vivid picture of how some of the earliest animals on earth progressed from egg to embryo to adult.

"Studying the developmental genetics of Nematostella is sort of like taking a time machine into the very distant past," said Gibson. "Our work allows us to ask what life looked like long ago -- hundreds of millions of years before the dinosaurs. How did ancient animals develop from egg to adult, and to what extent have the genetic mechanisms that guide embryonic development endured across millennia?"

Most contemporary animals, from insects to vertebrates, develop by forming a head-to-tail series of segments that assume distinct identities depending on their position. Within a given segment, there is a further axis of polarity that informs cells whether they are at the front or back of the segment. Collectively, this is referred to as segment polarization.

Shuonan He, Ph.D., a former predoctoral researcher from the Gibson Lab, uncovered genes involved during development of the sea anemone, Nematostella vectensis, that guide the formation of segments and others that direct segment polarity programs strikingly similar to organisms higher up the evolutionary tree of life, including humans.

"The significance is that the genetic instructions underlying the construction of extremely different animal body plans, for example, a sea anemone and a human, are incredibly similar," said Gibson. "The genetic logic is largely the same."

This new study builds upon a 2018 study published in Science from the Gibson Lab that showed that sea anemones have an internal bilateral symmetry early in development with eight radial segments. The study demonstrated that Hox genes -- master development genes that are crucial for human development -- act to delineate boundaries between segments and likely had an ancient role in segment construction.

The team's latest finding explores how segments form and what accounts for differences in their identities. Using spatial transcriptomics, or the differences in gene expression between segments, the team discovered hundreds of new segment-specific genes. These include two crucial genes that encode transcription factors that govern segment polarization under the control of Hox genes and are required for the proper placement of sea anemone muscles.

The astonishing diversity of organisms on Earth can be compared to the assembly of Legos. "Whether you construct a dinosaur, a sea anemone, or a human, many of the core genetic building blocks are largely the same despite drastically different animal forms," said Gibson.

This is the first time that scientists have evidence of a molecular basis for segment polarization in a pre-bilaterian animal. While extensively studied in bilateral species like fruit flies and humans, the idea that cnidarian animals possess segmentation was unexpected. Now, the team has evidence that these segments are also polarized.

"This provides further evidence that investigating a broad diversity of animals can have direct implications for understanding general principles, including those which apply to human biology," said Gibson. "Going one step further, by understanding the logic of sea anemone development and comparing it to what we see in vertebrates, we can also extrapolate back in time to understand how animals likely developed hundreds of millions of years ago."

Read more at Science Daily