About seven days after conception, something remarkable occurs in the clump of cells that will eventually become a new human being. They start to specialize. They take on characteristics that begin to hint at their ultimate fate as part of the skin, brain, muscle or any of the roughly 200 cell types that exist in people, and they start to form distinct layers.
Although scientists have studied this process in animals, and have tried to coax human embryonic stem cells into taking shape by flooding them with chemical signals, until now the process has not been successfully replicated in the lab. But researchers led by Ali Brivanlou, Robert and Harriet Heilbrunn Professor and head of the Laboratory of Stem Cell Biology and Molecular Embryology at The Rockefeller University, have done it, and it turns out that the missing ingredient is geometrical, not chemical.
“Understanding what happens in this moment, when individual members of this mass of embryonic stem cells begin to specialize for the very first time and organize themselves into layers, will be a key to harnessing the promise of regenerative medicine,” Brivanlou says. “It brings us closer to the possibility of replacement organs grown in petri dishes and wounds that can be swiftly healed.”
In the uterus, human embryonic stem cells receive chemical cues from the surrounding tissue that signal them to begin forming layers — a process called gastrulation. Cells in the center begin to form ectoderm, the brain and skin of the embryo, while those migrating to the outside become mesoderm and endoderm, destined to become muscle and blood and many of the major organs, respectively.
Brivanlou and his colleagues, including postdocs Aryeh Warmflash and Benoit Sorre as well as Eric Siggia, Viola Ward Brinning and Elbert Calhoun Brinning Professor and head of the Laboratory of Theoretical Condensed Matter Physics, confined human embryonic stem cells originally derived at Rockefeller to tiny circular patterns on glass plates that had been chemically treated to form “micropatterns” that prevent the colonies from expanding outside a specific radius. When the researchers introduced chemical signals spurring the cells to begin gastrulation, they found the colonies that were geometrically confined in this way proceeded to form endoderm, mesoderm and ectoderm and began to organize themselves just as they would have under natural conditions. Cells that were not confined did not.
By monitoring specific molecular pathways the human cells use to communicate with one another to form patterns during gastrulation — something that was not previously possible because of the lack of a suitable laboratory model — the researchers also learned how specific inhibitory signals generated in response to the initial chemical cues function to prevent the cells within a colony from all following the same developmental path.
The research was published June 29 in Nature Methods.
“At the fundamental level, what we have developed is a new model to explore how human embryonic stem cells first differentiate into separate populations with a very reproducible spatial order just as in an embryo,” says Warmflash. “We can now follow individual cells in real time in order to find out what makes them specialize, and we can begin to ask questions about the underlying genetics of this process.”
The research also has direct implications for biologists working to create “pure” populations of specific cells, or engineered tissues consisting of multiple cell types, for use in medical treatments. “These cells have a powerful intrinsic tendency to form patterns as they develop,” Warmflash says. “Varying the geometry of the colonies may turn out to be an important tool that can be used to guide stem cells to form specific cell types or tissues.”
Zach Veilleux | Eurek Alert!
Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel
Smelling the forest – not the trees
12.12.2018 | Universität Konstanz
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.
Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
12.12.2018 | Health and Medicine
12.12.2018 | Physics and Astronomy
12.12.2018 | Health and Medicine