Chicken and human hybrid
New research by a group of scientists from Rockefeller University led by Ali Brivanlou and Eric Siggia demonstrates a molecular scheme that determines the fate of a cell, as well as creates a platform for studying the early stages of human development.
Embryonic stem cells can differentiate into any of the types of cells in the body, be it bones or brain, lungs or liver. Special groups of cells have been found in amphibian and fish embryos that control the formation of early structures. These cells are called organizers, they release signaling molecules that cause the growth and certain development of other cells. Transplantation of host cells from one embryo to another causes the growth of the primary chord in the host body, from which bones and cartilage of the spine begin to form, and then the central nervous system is laid inside.
For ethical reasons, such experiments have not been conducted on human embryos, so scientists did not know if such organizers existed in humans. To find out, the group conducted a series of experiments with artificial human embryos – these are small clusters of cells, about one millimeter across, grown in a test tube from human embryonic stem cells. Artificial embryos are far from natural analogues, but still contain many of the cells and tissues inherent in living embryos.
Previous studies have shown that early embryonic development in animals such as mice and frogs is controlled by three different signaling pathways. Activation of these mechanisms in artificial human embryos has shown that the same molecular signals can stimulate development in human cells. If the signals were received in the correct sequence, the artificial embryos generated their own host cells. And yet there is a difference between how cells behave in a Petri dish and how they will behave inside a real embryo.
To confirm their initial results, the researchers inoculated artificial human embryos into live chicken embryos. Before that, they marked human cells with a fluorescent marker, which made it possible to accurately track the cells under a microscope.
Researchers have never been able to successfully graft human embryonic cells into an early bird embryo. In this experiment, human cells began laying the primary chord and neural tube – a fact that confirmed the presence of host cells.
The origin of these structures turned out to be surprising. The primary chord, from which the cartilage and bone tissue of the spine is formed, consisted of human cells, and the nerve tissue of the spinal cord developing inside consisted exclusively of chicken cells.
Human host cells (red), after grafting into a chicken embryo, generate axial structures (blue) and other tissues. Source: The Rockefeller University.
Thus, human cells were able not only to create new structures in the chicken embryo, but also to stimulate host cells to differentiate into nerve tissue.
Understanding how undifferentiated stem cells become a certain type of tissue is of great importance for regenerative medicine, the essence of which is the use of stem cells for the treatment and restoration of damaged tissues.
The technology by which Brivanlu and his group inoculated cells into live chicken embryos is a powerful new tool for studying the early stages of human development. They are already using it in other studies. By discovering new details of the process of differentiation of stem cells into normal tissue, the approach should help scientists understand when and how development can go wrong from the first moments of the embryo's life.
This, in turn, will create new ways to prevent miscarriages and birth defects, as well as methods of treating diseases from cancer to diabetes.
Article I. Martyn et al. Self-organization of a human organizer by combined Wnt and Nodal signaling is published in the journal Nature.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of The Rockefeller University: A first look at the earliest decisions that shape a human embryo.