In an impressive achievement published in Nature Communications, a global team of scientists has successfully created mouse stem cells that can develop into a fully formed mouse. They utilized genetic components from a unicellular organism, sharing a common ancestor that predates all animals, to accomplish this feat. This important discovery changes our comprehension of the genetic foundations of stem cells and illuminates the evolutionary connections between modern animals and their ancient single-celled ancestors.
In a groundbreaking experiment reminiscent of science fiction, Dr. Alex de Mendoza from Queen Mary University of London, alongside researchers from The University of Hong Kong, employed a gene from choanoflagellates, a single-celled organism closely related to animals, to produce stem cells that eventually gave rise to a living mouse. Choanoflagellates are recognized as the closest living relatives of animals, with their genomes containing versions of the Sox and POU genes, which are essential for enabling pluripotency — the ability of cells to differentiate into any cell type — in mammalian stem cells. This surprising finding contradicts the long-held belief that these genes evolved solely within animals.
“Creating a mouse with molecular tools from our single-celled relatives represents an incredible continuity of function across nearly a billion years of evolution,” stated Dr. de Mendoza. “Our research suggests that significant genes linked to stem cell development could have emerged much earlier than stem cells themselves, potentially contributing to the evolution of multicellular life as we know it today.”
The Nobel Prize awarded to Shinya Yamanaka in 2012 revealed that stem cells can be derived from “differentiated” cells by activating four key factors, including one Sox gene (Sox2) and a POU gene (Oct4). In the current study, through collaboration with Dr. Ralf Jauch’s laboratory at The University of Hong Kong / Centre for Translational Stem Cell Biology, the team introduced the choanoflagellate Sox genes into mouse cells, effectively substituting the native Sox2 gene and inducing a reprogramming into a pluripotent stem cell state. To confirm the functionality of these reprogrammed cells, they were injected into a developing mouse embryo. The resulting chimeric mouse exhibited characteristics from both the original embryo and the lab-generated stem cells, such as patches of black fur and dark eyes, demonstrating the essential role of these ancient genes in aligning stem cells with the animal’s developmental processes.
The research outlines how primitive versions of the Sox and POU proteins, which bind to DNA and regulate other genes, were utilized by unicellular ancestors for functions that would eventually become crucial for stem cell formation and the development of animals. “While choanoflagellates do not have stem cells as they are unicellular organisms, they possess these genes that likely govern fundamental cellular functions, which multicellular animals may have later adapted for constructing sophisticated bodies,” Dr. de Mendoza noted.
This innovative insight highlights the evolutionary flexibility of genetic mechanisms and suggests that early life forms may have employed similar strategies to facilitate cellular specialization long before true multicellular organisms appeared, also emphasizing the significance of gene recycling in evolution.
This discovery extends its relevance beyond evolutionary biology, potentially leading to breakthroughs in regenerative medicine. By enhancing our comprehension of the evolution of stem cell mechanisms, scientists might uncover new ways to refine stem cell therapies and improve reprogramming techniques for treating diseases or healing damaged tissues.
“Exploring the ancient origins of these genetic mechanisms enables us to innovate with a sharper understanding of how pluripotency processes can be adjusted or enhanced,” Dr. Jauch remarked, adding that future advancements could originate from experimenting with synthetic variants of these genes that could outperform native animal genes in specific situations.
