Scientists generate key life events of an artificial mouse embryo created from stem cells



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The creation of artificial embryos took a step forward after an international team of researchers had used mouse stem cells to produce embryonic artificial structures capable of "gastrulation," a key step in the life of any embryo.

The team, led by Professor Magdalena Zernicka-Goetz at the University of Cambridge, previously created a much simpler structure resembling a cultured mouse embryo, using two types of stem cells – the "mother cells" of the body – and Now, in a study published today in Nature Cell Biology Professor Zernicka-Goetz and his colleagues developed embryonic-like structures, using not only two but three types of stem cells that allow them to reconstruct a process known as gastrulation, an essential step in which embryonic cells self-organize into the correct structure to form an embryo [19659005OnceamammalianegghasbeenfertilizedbyaspermitdividesseveraltimestogenerateasmallfloatingballcomprisingthreetypesofstemcellsAtthestageofdevelopmentknownasthe"blastocyst"stagetheparticularstemcellsthatwilleventuallyformthefuturebody-theembryonicstemcells(ESCs)-clusterwithintheembryotowardsoneendTheothertwotypesofblastocyststemcellsareextra-embryonictrophoblasticstemcells(TSCs)whichwillformtheplacentaandprimitiveendodermalstemcells(PESCs)thatwillformtheyolksactherebyensuringthedevelopmentoffetalorgans

In March 2017, Professor Zernicka-Goetz and his colleagues published a study describing how, using a combination of these genetically modified MS and TSCs, as well as a 3-D jelly scaffold known as the extracellular matrix name, they were able to develop a structure capable of badembling and whose development and architecture closely resembled the natural embryo. There was a remarkable degree of communication between the two types of stem cells: in a sense, the cells were telling themselves where to place themselves in the embryo.

However, a key milestone in the life of embryo-gastrulation, described by the eminent biologist Lewis Wolpert as "the most important moment of your life – was missing." Gastrulation is the point where the Embryo pbades from a single layer to three layers: an inner layer (endoderm), an intermediate layer (mesoderm). ) and the outer layer (endoderm), determining which tissues or organs will then develop the cells.

"Correct gastrulation in normal development is only possible if you have all three types of stem cells." To reconstruct this complex dance, we had to add the third missing stem cell, "explains Professor Zernicka. Goetz. "By replacing the jelly that we used in previous experiments with this third type of stem cells, we were able to generate structures By adding the PESCs, the team could see their" embryo "undergo gastrulation, s 'organizing in three body layers that all animals possess.The timing, architecture and patterns of gene activity are reflected.' Our artificial embryos have undergone the most important event of life in the dish of culture, "adds Professor Zernicka-Goetz," They are now extremely close to real embryos, and to develop further they should be implanted in the body. of the mother or an artificial placenta. "

The researchers say that they should now be able to better understand how the three types of stem cells interact to allow the embryo to develop, experimentally altering biological pathways in a type of cell and seeing how this affects the behavior of one or both cell types.

"We can now try to apply this to the equivalent human stem cell types and thus study the very first events development of the human embryo without having to use natural human embryos, "explains Professor Zernicka-Goetz

. By applying these studies side by side, it should be possible to learn a lot about the fundamentals. In fact, such comparisons should allow scientists to study the events that occur beyond day 14 in human pregnancies, but without using 14-day human embryos, British law allows embryos "The first steps in embryo development are when a large part of the pregnancies are lost and yet it's a step we know very little," says Professor Zernicka. -Goetz. "Now we have a way to simulate embryonic development in the culture dish, so it should be possible to understand exactly what is going on during this remarkable period in the life of an embryo, and why sometimes this process fails. . "


Learn more:
Scientists create an artificial mouse embryo from stem cells for the first time

More information:
Berna Sozen et al., Self-badembly of embryonic stem cell types and two types of extra-embryonic stem cells in gastric embryonic structures, Nature Cell Biology (2018). DOI: 10.1038 / s41556-018-0147-7

Journal Reference:
Cell biology of nature

Source:
University of Cambridge

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