Researchers from the University of California, Berkeley, have found a way to reprogram mouse embryonic stem cells so they exhibit developmental characteristics resembling those of fertilized eggs, or even zygotes.
These “totipotent-like” come cells are able to generate not only all cell types inside a developing embryo, but also cell types that facilitate nutritional exchange between the embryo and the mother.
For the time being, the new stem cell lines UC Berkeley researchers possess created will help scientists understand the first molecular decisions produced in the early embryo. Ultimately, however , these insights could broaden the particular repertoire of tissues that can be generated from stem cellular material, with significant implications for regenerative medicine and come cell-based therapy.
A fertilized egg is definitely thought to possess full developmental potential, able to generate almost all cell types required for embryo gestation, including the developing embryo and its extra-embryonic tissues. A unique feature of placental mammals, extra-embryonic tissues such as the placenta and yolk sac are usually vital for nutrient and waste exchange between the baby and mother.
By contrast, most embryonic plus induced pluripotent stem cells are more restricted in their developing potential, able to form embryonic cell types, but not extra-embryonic tissues. The ability of a fertilized egg to generate both wanting and extra-embryonic tissues is referred to as “totipotency, ” an supreme stem cell state seen only during the earliest phases of embryonic development.
“Studies on wanting development greatly benefit from the culture system of embryonic stem tissue and, more recently, induced pluripotent stem cells. These fresh systems allow scientists to dissect key molecular paths that specify cell fate decisions in embryonic growth, ” said team leader Lin He, an UC Berkeley associate professor of molecular and cell the field of biology. “But the unique developmental potential of a zygote, formed just after the sperm and egg meet, is very, very difficult to analyze, due to limited materials and the lack of a cell-culture fresh system. ”
He’s new study not just reveals a novel mechanism regulating the “totipotent-like” come cell state, but also provides a powerful cell-culture system to help study totipotency.
She and her co-workers reported their research online Jan. 12 in advance of printing publication in the journal Science .
MicroRNAs and stem cells
Embryonic stem (ES) cells, harvested from three-and-a-half-day-old mouse embryos or five-and-a-half-day-old human embryos, are known as pluripotent because they can become any of the thousands of cell types in your body. They have generated excitement over the past few decades because researchers can study them in the laboratory to discover the hereditary switches that control the development of specialized tissues in the embryo and fetus, and also because of their potential to replace body tissue that have broken down, such as pancreatic cells in those with diabetes or heart muscle cells in those with congestive cardiovascular failure. These stem cells can also let researchers research the early stages of genetic disease.
Rather than harvesting them from embryos, scientists can also obtain pluripotent stem cells by treating mature somatic cells having a cocktail of transcription factors to regress them so they are nearly as flexible as embryonic stem cellular material. These artificially derived stem cells are called induced pluripotent stem (iPS) cells.
Neither ES neither iPS cells, however , are as flexible as the original fertilized egg, which can form extra-embryonic as well as embryonic tissues. When embryonic stem cells are harvested from a mouse or even human embryo, the cells have already committed to either an wanting or an extra-embryonic lineage.
MicroRNAs are usually small, non-coding RNAs that do not translate into proteins, however have a profound impact on gene expression regulation. He plus her colleagues found that a microRNA called miR-34a seems to be a brake preventing both ES and iPS cellular material from producing extra-embryonic tissues. When this microRNA had been genetically removed, both ES and iPS cells could expand their developmental decisions to generate embryo cell varieties as well as placenta and yolk sac linages. In their tests, about 20 percent of embryonic stem cells deficient the microRNA exhibited expanded fate potential. Furthermore, this particular effect could be maintained for up to a month in cell tradition.
“What is quite amazing is that manipulating only a single microRNA was able to greatly expand cell fate choices of embryonic stem cells, ” He said. “This finding not only identifies a new mechanism that regulates totipotent stem cells, but also reveals the importance of non-coding RNAs within stem cell fate. ”
Additionally , within this study, He’s group discovered an unexpected link between miR-34a and a specific class of mouse retrotransposons. Long thought to be “junk DNA, ” retrotransposons are pieces of ancient international DNA that make up a large fraction of the mammalian genome. For decades, biologists assumed that these retrotransposons serve no purpose during regular development, but He’s findings suggest they may be closely associated with the decision-making of early embryos.
“An important open question is whether these retrotransposons are true drivers of developmental decision making, ” said Todd MacFanlan, a co-author of the current study and a researcher in the Eunice Kennedy Shriver National Institute of Child Into the Human Development in Bethesda, Maryland.