For the first time, scientists created mouse stem cells from the genes of a single-celled life form.
Stem cells are special because they can make more of themselves and also transform into other cells with different functions.
He only had three sequenced genomes to search at the time, but initial analyses didn’t show any of those special stem cell genes.
Through a series of experiments, Jauch and postdoctoral fellow Ya Gao introduced the genes from the choanoflagellate into mouse cells.
The team also introduced the Pou gene found in the choanoflagellate to the mouse cells, but it did not induce stem cells.
The animal kingdom started to split off from single-celled organisms about 700 million years ago. In order to test the molecular tools that scientists have discovered that could have aided the leap, they created a mouse from our unicellular ancestor.
For the first time, researchers used the genes of a single-celled organism to create mouse stem cells. Because they can divide into other cells with distinct roles and produce more of themselves, stem cells are unique. According to research published in Nature Communications, the team used these newly created stem cells to assist in the development of a living, breathing mouse from a developing embryo.
Scientists believed that the genes that enabled stem cells to divide and specialize only existed in animals, and most definitely not in a group of single-celled protists from nearly a billion years ago, so the discovery was unexpected.
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“The stem cell molecular toolkit is much older than we previously thought,” said Ralf Jauch, a University of Hong Kong stem cell biologist and study author. These molecular instruments predate even animal stem cells. “.”.
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Learning about our natural evolution to become multicellular can also “make better stem cell models,” which could help reverse aging or disease, according to Jauch.
The formula for animal stem cells.
The number of cells is not the only distinction between protists and animals. All functions are carried out within a cell by protists, which are usually unicellular microscopic organisms that are not fungi, plants, or animals. Nonetheless, animals are the best delegators because they assign different tasks to different cells.
According to Alex de Mendoza, a study author at Queen Mary University of London, “we know that animals, most of them have stem cells because it’s something that you need.”. “Cells that can divide and produce new cells are what you need.”. “”.
What it takes to produce a stem cell in an animal was clarified by the 2012 Nobel Prize in medicine. Six years prior, stem cell researcher Shinya Yamanaka discovered that adult cells could be reprogrammed into stem cells by introducing four specific genes, referred to as the Yamanaka factors: Sox2, Pou5F1, Klf4, and Myc.
Because it didn’t seem necessary for a unicellular organism to have stem cell capabilities, most people thought those genes were exclusive to the animal kingdom. As part of his PhD research, de Mendoza even looked for these genes in protists and other unicellular organisms around ten years ago. Initially, he was only able to search three sequenced genomes, but none of those unique stem cell genes were found.
Then, new information revealed a shocking discovery. With more information at their disposal, de Mendoza and his associates conducted another genome search in 2022. After looking through roughly 30 sequences, they discovered a few that contained variations of these animal-found Yamanaka factors, which are members of the “Sox” and “Pou” gene families.
“We thought that was really strange when we found them,” de Mendoza remarked. “We were surprised to see them. “”.
A mouse created from genes that predate animal life.
The team found the genes in a protist known as a choanoflagellate, or “collar” flagellate, which is roughly the size of a dust particle. Although they might not appear so at first glance, these protists are the closest living relatives of the animal kingdom. Using a whip (or its flagella), they move through the water like tiny tadpoles and collect bacteria to put in their feeding collar.
Although the exact appearance of the first multicellular animal is unknown, choanoflagellates may provide information about the evolution and fundamental cell biology of that organism.
Some researchers believe sponges may have been the first multicellular animal because choanoflagellates resemble a type of sponge cell. However, newer evidence indicated that it might have been comb jelly.
De Mendoza and his associates looked through the sequences of 22 different species of choanoflagellates for the study, but they “only found 2 with convincing hits.”. The group aimed to determine whether the recently discovered Sox and Pou genes from choanoflagellates would function similarly to those in animals.
The protist genes weren’t guaranteed to function similarly. Mammals have about 20 different Sox genes, including Sox2, a unique variant that is crucial for programming mammalian stem cells. It’s unclear, though, how the molecular machinery would function because the choanoflagellate Sox existed before all 20 mammalian copies.
The genes from the choanoflagellate were inserted into mouse cells by Jauch and postdoctoral fellow Ya Gao through a series of experiments. They successfully reprogrammed the cells to the stem cell state by substituting a mouse’s Sox2 gene with a choanoflagellate gene that is similar. They injected the reprogrammed cells into a developing mouse embryo to verify that it was successful. In addition to the lab-induced stem cells, which had genetic markers like dark eyes and black fur patches, the mouse developed the physical traits of its original embryo.
We can exchange parts with creatures that don’t appear to be related to us. Then all of a sudden, they can be utilized to create things that we think are extremely important and complex,” de Mendoza stated.
The study’s Frankenstein-style experiments weren’t all successful. Although it did not stimulate stem cells, the team also added the Pou gene from the choanoflagellate to the mouse cells. According to de Mendoza, the problem was that the unicellular Pou gene attached to the DNA differently than other animal Pou genes.
According to the experiments, Pou required additional evolutionary tweaking before it could fulfill its current role in contemporary animals, according to Jauch.
To go even farther, the team looked at the appearance of our common ancient ancestor, which may have been of animals and choanoflagellates. Colleagues at the Max Planck Institute for Terrestrial Microbiology created a molecular time machine to travel back in time to long-extinct ancestors using sophisticated computer algorithms. Despite not creating a mouse using these ancient sequences, the team discovered that these molecular characteristics for Sox proteins were present. This discovery demonstrated that the ability is genuinely ancestral and existed before animals evolved.
“This very elegant body of work has very exciting, but not surprising, findings,” said Sandie Degnan, a biology professor at the University of Queensland who did not participate in the study. Unicellular organisms, in my opinion, must be a “jack of all trades,” since a single cell must be able to fulfill all of the requirements for survival. “”.
The study supports and expands on Degnan and her colleagues’ theory that the earliest animal cells had the capacity to change between several states, much like contemporary stem cells. According to her, it makes sense that the earliest animal cells, our last common ancestor, had innate adaptability that might have enabled them to handle difficulties posed by their surroundings. It is probable that natural selection would favor this advantage over cells that remained in a fixed state.
Daniel Richter, an evolutionary biologist who did not participate in the study, stated that we are still impressed by our close animal relatives. This study and other recent research in this area demonstrate that we underestimate the abilities of our last common ancestor with choanoflagellates.
“It blurs the line between artificial definitions of what it means to be’simple’ versus ‘complex,'” according to Richter, a researcher at the Institute of Evolutionary Biology in Barcelona.
The team is still baffled as to why our ancient ancestor or a choanoflagellate would possess this gene capability. Although multicellular animals repurposed it to create complex bodies, De Mendoza suggested that they might have used it to control basic processes like cell proliferation.
“Inventing isn’t always necessary for evolution,” de Mendoza stated. “Usually, you start with whatever you have and then use mostly recycled parts to create something new.”. “”.
