Tag Archives: stem cell research

Coelacanth (a living fish fossil) may provide clue to making artificial organs for transplantation

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An ancient fish called a ‘living fossil’ has helped researchers understand the basics of stem cells. This will further stem cell research and be a step in the direction of creating artificial organs. The coelacanth fish is 400 million years old. Photo: Canva. Courtesy: university of Copenhagen

A December 12, 2022 University of Copenhagen press release (also on EurekAlert) describes work which may have an impact on organ transplants,

A beating heart. A complicated organ that pumps blood around the body of animals and humans. Not exactly something you associate with a Petri dish in a laboratory.

But that may change in the future, and save the lives of people whose own organs fail. And the research is now one step closer to that.

To design artificial organs you first have to understand stem cells and the genetic instructions that govern their remarkable properties.

Professor Joshua Mark Brickman at the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) has unearthed the evolutionary origins of a master gene that acts on a network of genes instructing stem cells.

“The first step in stem cell research is to understand the gene regulatory network that supports so-called pluripotent stem cells. Understanding how their function was perfected in evolution can help provide knowledge about how to construct better stem cells,” says Joshua Mark Brickman.

Pluripotent stem cells are stem cells that can develop into all other cells. For example, heart cells. If we understand how the pluripotent stem cells develop into a heart, then we are one step closer to replicating this process in a laboratory.

What are stem cells?

Stem cells are non-specialized cells found in all multicellular organisms. Stem cells have two properties that distinguish them from other cell types. On the one hand, stem cells can undergo an unlimited number of cell divisions (mitoses), and on the other hand, stem cells have the ability to mature (differentiate) into several cell types.

A pluripotent stem cell is a cell that can develop into any other cell, such as a heart cell, hair cell or eye cell.

A ‘living fossil’ is the key to understanding stem cells

The pluripotent property of stem cells – meaning that the cells can develop into any other cell – is something that has traditionally been associated with mammals.

Now Joshua Mark Brickman and his colleagues have found that the master gene that controls stem cells and supports pluripotency also exists in a fish called coelacanth. In humans and mice this gene is called OCT4 and they found that the coelacanth version could replace the mammalian one in mouse stem cells.

In addition to the fact that the coelacanth is in a different class from mammals, it has also been called a ‘living fossil,’ since approximately 400 million years ago it developed into the form it has today. It has fins shaped like limbs and is therefore thought to resemble the first animals to move from the sea onto land.

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

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 already existed early in evolution, potentially as far back as 400 million years ago.”

And by studying the network in other species, such as this fish, the researchers can distill what the basic concepts that support a stem cell are.

“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 start to separate what is really important for stem cells and use that to improve how you grow stem cells in a dish,” says PhD student Elena Morganti.

Sharks, mice and kangaroos

In addition to the researchers finding out that the network around stem cells is much older than previously thought, and found in ancient species, they also learned how exactly evolution has modified the network of genes to support pluripotent stem cells.

The researchers looked at the stem cell genes from over 40 animals. For example sharks, mice and kangaroos. The animals were selected to provide a good sampling of the main branch points in evolution.

The researchers used artificial intelligence to build three-dimensional models of the different OCT4 proteins. The researchers could see that the general structure of the protein is maintained across evolution. While the regions of these proteins known to be important for stem cells do not change, species-specific differences in apparently unrelated regions of these proteins alter their orientation, potentially affecting how well it supports pluripotency.

“This a very exciting finding about evolution that would not have been possible prior to the advent of new technologies. You can see it as evolution cleverly thinking, we don 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,” says Joshua Mark Brickman.

…

The study is a collaborative project spanning Australia, Japan and Europe, with vital strategic partnerships with the groups of Sylvie Mazan at the Oceanological Observatory of Banyuls-sur-Mer in France and professor Guillermo Montoya at Novo Nordisk Foundation Center for Protein Research at University of Copenhagen.

Caption: Coelacanth-fish and other animals. Credit: By Woranop Sukparangsi Courtesy: University of Copenhagen

Here’s a link to and a citation for the paper,

Evolutionary origin of vertebrate OCT4/POU5 functions in supporting pluripotency by Woranop Sukparangsi, Elena Morganti, Molly Lowndes, Hélène Mayeur, Melanie Weisser, Fella Hammachi, Hanna Peradziryi, Fabian Roske, Jurriaan Hölzenspies, Alessandra Livigni, Benoit Gilbert Godard, Fumiaki Sugahara, Shigeru Kuratani, Guillermo Montoya, Stephen R. Frankenberg, Sylvie Mazan & Joshua M. Brickman. Nature Communications volume 13, Article number: 5537 (2022) DOI: https://doi.org/10.1038/s41467-022-32481-z Published: 21 September 2022

This paper is open access.

Perceptions of Promise, an art/science show at Glenbow Museum, Alberta

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The art/science show, Perceptions of Promise, at Alberta’s Glenbow Museum in Calgary features stem cell research, ethics, and art. It’s the outcome of a workshop that was held May 2010 in Alberta. Here’s an image from the show,

Derek Besant, Still from Metamorphosis Theory, 2010. Copy obtained from Glenbow Museum website.

An article by Jef Akst, Controversy on display; A Canadian art exhibit takes a different look at the ongoing debate surrounding human stem cell research,  in The Scientist provides an interview with one of the organizers of the show, Timothy Caulfield, a bioethicist at the Health Law Institute of the University of Alberta,

Over the last couple of years, Caulfield [Timothy] has worked with his brother Sean, a professor of art design also at the University of Alberta, to brainstorm ways to combine their interests in art, science, and society. The brothers’ first brainchild, a 2009 art show in Alberta called Imagining Science, explored legal and ethical issues surrounding biotechnological advances, such as cloning and genetic testing

While they were happy with the exhibition’s success, they felt there were plenty more issues left to cover. “Many of the people involved thought this conversation isn’t over,” Sean says. “It’s kind of just beginning.” So they decided to do it again, this time focusing on the contentious issues surrounding stem cell research.

Following the tradition of their first exhibition, they organized a workshop that brought together scientists, social commentators, and artists to present their work and represent diverse perspectives on stem cell research.

Here’s an excerpt from a posting by one of the participants, Matthew Nisbet, an associate professor in the School of Communication at American University. (At the time of writing, his blog was called Framing Science, Nisbet has since changed his blogging focus and has moved and renamed his blog, Age of Engagement; all the archival posts for Framing Science are included.) From Nisbet’s archived May 5, 2010 posting on Age of Engagement,

Last week I traveled to the Canadian Rockies to participate in a unique workshop organized by the University at Alberta that focused on the shared perspectives and collaborations among artists, scientists, ethicists, and social scientists. The workshop was the second in a series organized by brothers Sean Caulfield and Timothy Caulfield, professors of Art and Law respectively at the University of Alberta.

In 2009, the first workshop resulted in the “Imagining Science” exhibit at the Art Gallery of Alberta and a book by the same title. The critically acclaimed initiative highlighted the emerging genre of “bio art,” which Tim Caulfield in his contribution to the award-winning book describes as “a field of artistic inquiry that both utilizes the techniques of biotechnology and serves as a medium of reflection on the societal implications of the research.”

Here’s an example of a collaboration from the 2010 workshop which has resulted in the Perceptions of Promise show (from the article by Jef Akst),

Paul Cassar, a doctoral student at the University of Toronto who works with mouse embryonic stem cells, took an even more hands-on approach to his collaboration with artist Daniela Schlüter — he actually drew some scientific schematics from which Schlüter created her mixed media drawings.

“By no means am I a good drawer,” Cassar says. “Even my sketches could have been done better by a three year old,” he jokes. But when Schlüter overlaid her own drawings, she was able to “create this story to contrast some of these tensions [of] where we are now with this stem cell debate,” he says. “I think is a really neat example of how science can be inspiring to other creative minds.”

There’s also video of the show featuring the images,

Finally, the Perceptions of Promise website and the Glenbow Museum website.