Scientists have engineered a hybrid mouse with a gene that predates all animal life. The team replaced a single gene in the mouse stem cells with a version from an ancient, single-celled ancestor, and successfully grew healthy live mice from it.
Stem cells are famously able to differentiate into multiple types of cells in the body. In 2006, Japanese scientists discovered a technique to convert mature cells back into stem cells, which they called induced pluripotent stem cells (iPSCs). This breakthrough paved the way for a range of new potential regenerative therapies.
That original team found that iPSCs can be made by tweaking just four genes, which were named Yamanaka factors. In the new study, researchers from Queen Mary University of London and the University of Hong Kong swapped out the mouse version of one of those genes for a much older one.
Choanoflagellates are the closest single-celled relative to the branch of life that gave rise to animals. Being single-celled, they have no need for stem cells, but still have some of the genes that code for them in animals, so the team wanted to investigate whether those genes would perform the same role.
The researchers started by making mouse iPSCs the usual way, except for one change: they swapped out Sox2, one of the Yamanaka factors, for the corresponding Sox gene from choanoflagellates. These “hybrid” iPSCs were then injected into a developing mouse embryo.
To make it clear if the experiment had worked, the researchers engineered those iPSCs to produce physical traits like dark eyes and patches of black fur. And sure enough, the mouse that grew from that embryo was a chimera, displaying these traits along with those of the original embryo donor.
It’s an extraordinary result, showing that the modern stem cell functions of these genes were primed and ready long before stem cells were even “invented.” The researchers suggest that the choanoflagellates probably used them to control other basic cellular processes, and multicellular organisms later adapted them to their current purpose.
“By successfully creating a mouse using molecular tools derived from our single-celled relatives, we’re witnessing an extraordinary continuity of function across nearly a billion years of evolution,” said Alex de Mendoza, corresponding author of the study. “The study implies that key genes involved in stem cell formation might have originated far earlier than the stem cells themselves, perhaps helping pave the way for the multicellular life we see today.”
The researchers say the discovery could help inform new regenerative medicine therapies.
The research was published in the journal Nature Communications.
Source: Queen Mary University of London
