This discovery is published today in EMBO, the European Molecular Biology Organization journal.
"These findings not only have implications for stem cell research and the study of how embryos grow and take shape, but also for cancer therapy," said the senior author of the study, Dr. Hannele Ruohola-Baker, University of Washington professor of biochemistry. The study was collaborative among several research labs in Seattle.
The metabolic transition they discovered occurs very early as the mouse embryo, barely more than a speck of dividing cells, implants in the mother's uterus. The change is driven by low oxygen conditions, Ruohola-Baker explained.
The researchers also saw a specific type of biochemical slowdown in the stem cells' mitochondria the cells' powerhouses. The phenomenon previously was associated with aging and disease. This was the first example of the same downshift controlling normal early embryonic development.
"This downshift coincides with the time when the germ line, the keeper of the genome for the next generation, is set aside," Ruohola-Baker said.. "Hence reduction of mitochondrial reactive oxygen species may be nature's way to protect the future."
Embryonic stem cells are called pluripotent because they have the ability to renew themselves and have the potential to become any cell in the body. Self-sustaining and versatile are qualities necessary for the growth, repair and maintenance of the body and for regenerative medicine therapies.
Although they share these sought-after qualities, "Pluripotent stem cells come in several flavors," Ruohola-Baker explained. They differ in subtle ways that expand or shrink their capacities as the raw living material from which animals are shaped.
There's a big reason why the researchers wanted to understand the distinction between the stem cells that make up the inner cell mass of the free-floating mouse embryo, and those in the epiblast, or implantation stage. Mouse embryonic cells at the epiblast stage more closely resemble human embryonic stem cells -- and cancer cells.
Human stem cells and mouse epiblast stem cells have lower mitochondrial respiration activity than do earlier stage mouse stem cells. This reduction occurs despite the fact that the later stage stem cells have more mature mitochondria. The researchers confirmed that certain genes that control mitochondria are turned down during the transition from inner cells mass to epiblast cells.
Instead, the transitioning cells obtain their energy exclusively from breaking down a sugar, glucose. In contrast, the earlier stage mouse embryonic stem cells have more energy options, dynamically switching from mitochondrial respiration to glucose breakdown on demand.
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Embryonic stem cells shift metabolism in cancer-like way upon implanting in uterus