Scientists from Queen Mary University of London and the University of Hong Kong have created mouse stem cells capable of generating a fully developed mouse using genetic tools from a unicellular organism, with which we share a common ancestor that predates animals.
Choanoflagellate Sox can induce pluripotency in mammalian cells. Image credit: Gao et al., doi: 10.1038/s41467-024-54152-x.
Queen Mary University of London researcher Alex de Mendoza and colleagues used a gene found in choanoflagellates, a single-celled organism related to animals, to create stem cells which they then used to give rise to a living, breathing mouse.
Choanoflagellates are the closest living relatives of animals, and their genomes contain versions of the genes Sox and POU, known for driving pluripotency — the cellular potential to develop into any cell type — within mammalian stem cells.
This unexpected discovery challenges a longstanding belief that these genes evolved exclusively within animals.
“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,” Dr. de Mendoza said.
“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 2012 Nobel prize to Shinya Yamanaka demonstrated that it is possible to obtain stem cells from differentiated cells just by expressing four factors, including a Sox (Sox2) and a POU (Oct4) gene.
In the new research, Dr. de Mendoza and co-authors introduced choanoflagellate Sox genes into mouse cells, replacing the native Sox2 gene achieving reprogramming towards the pluripotent stem cell state.
To validate the efficacy of these reprogrammed cells, they were injected into a developing mouse embryo.
The resulting chimeric mouse displayed physical traits from both the donor embryo and the lab induced stem cells, such as black fur patches and dark eyes, confirming that these ancient genes played a crucial role in making stem cells compatible with the animal’s development.
The study traces how early versions of Sox and POU proteins, which bind DNA and regulate other genes, were used by unicellular ancestors for functions that would later become integral to stem cell formation and animal development.
“Choanoflagellates don’t have stem cells, they’re single-celled organisms, but they have these genes, likely to control basic cellular processes that multicellular animals probably later repurposed for building complex bodies,” Dr. de Mendoza said.
“This novel insight emphasizes the evolutionary versatility of genetic tools and offers a glimpse into how early life forms might have harnessed similar mechanisms to drive cellular specialization, long before true multicellular organisms came into being, and into the importance of recycling in evolution.”
“This discovery has implications beyond evolutionary biology, potentially informing new advances in regenerative medicine.”
A paper on the findings was published in the journal Nature Communications.
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Y. Gao et al. 2024. The emergence of Sox and POU transcription factors predates the origins of animal stem cells. Nat Commun 15, 9868; doi: 10.1038/s41467-024-54152-x
This article is based on a press-release provided by Queen Mary University of London.
