An international team of scientists has achieved a groundbreaking milestone by creating mouse stem cells capable of generating a fully developed mouse. This was accomplished using genetic tools from choanoflagellates, a single-celled organism considered the closest living relative of animals.
The team, led by Dr. Alex de Mendoza of Queen Mary University of London and collaborators from The University of Hong Kong, discovered that choanoflagellates possess genes (Sox and POU) known to drive pluripotency in mammalian stem cells. This challenges the long-held belief that these genes evolved exclusively in animals, offering new insights into the evolutionary relationship between animals and their ancient, single-celled ancestors.
The study reshapes our understanding of the genetic origins of stem cells.
By creating a mouse using molecular tools derived from our single-celled relatives, scientists have demonstrated an extraordinary continuity of function spanning nearly a billion years of evolution. This study suggests that key genes involved in stem cell formation may have originated long before the emergence of true stem cells, potentially playing a crucial role in the development of multicellular life.
Building on Shinya Yamanaka’s 2012 Nobel-winning discovery that stem cells can be derived from differentiated cells by expressing four factors, including Sox2 and Oct4, new research has taken this concept further. In collaboration with Dr. Ralf Jauch’s lab at The University of Hong Kong, researchers introduced choanoflagellate Sox genes into mouse cells, replacing the native Sox2 gene and successfully reprogramming them to a pluripotent state.
Scientists investigated how multicellular life evolves from scratch
The reprogrammed cells were then injected into a developing mouse embryo, resulting in a chimeric mouse with traits from both the donor embryo and the induced stem cells. This confirms the ancient genes’ role in enabling stem cell compatibility with animal development. This study highlights how early versions of Sox and POU proteins, used by unicellular ancestors for gene regulation, became key to stem cell formation and the development of multicellular animals.
Dr de Mendoza said, “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.”
This discovery highlights the evolutionary flexibility of genetic tools and suggests that early life forms may have used similar mechanisms for cellular specialization long before multicellular organisms evolved.
It also emphasizes the role of “recycling” in evolution, where ancient genetic components are repurposed. Beyond evolutionary biology, the findings could inform advances in regenerative medicine, offering new ways to optimize stem cell therapies and improve cell reprogramming techniques for disease treatment and tissue repair.
Dr Jauch said, “Studying the ancient roots of these genetic tools lets us innovate with a clearer view of how pluripotency mechanisms can be tweaked or optimised. Advancements could arise from experimenting with synthetic versions of these genes that might perform even better than native animal genes in certain contexts.”
Journal Reference:
- Gao, Y., Tan, D.S., Girbig, M. et al. The emergence of Sox and POU transcription factors predates the origins of animal stem cells. Nat Commun 15, 9868 (2024). DOI: 10.1038/s41467-024-54152-x
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