A stem cell–derived human embryo model at a developmental stage equivalent to that of a day 14 embryo. The model has all the compartments that define this stage: the yolk sac (yellow) and the part that will become the embryo itself, topped by the amnion (blue) – all enveloped by cells that will become the placenta (pink). Credit: Weizmann Institute of Science
A research team headed by Prof. Jacob Hanna at the Weizmann Institute of Science has created complete models of human embryos from stem cells cultured in the lab—and managed to grow them outside the womb up to day 14. As reported today in Nature, these synthetic embryo models had all the structures and compartments characteristic of this stage, including the placenta, yolk sac, chorionic sac and other external tissues that ensure the models’ dynamic and adequate growth.
Cellular aggregates derived from human stem cells in previous studies could not be considered genuinely accurate human embryo models, because they lacked nearly all the defining hallmarks of a post-implantation embryo. In particular, they failed to contain several cell types that are essential to the embryo’s development, such as those that form the placenta and the chorionic sac. In addition, they did not have the structural organization characteristic of the embryo and revealed no dynamic ability to progress to the next developmental stage.
Given their authentic complexity, the human embryo models obtained by Hanna’s group may provide an unprecedented opportunity to shed new light on the embryo’s mysterious beginnings. Little is known about the early embryo because it is so difficult to study, for both ethical and technical reasons, yet its initial stages are crucial to its future development.
During these stages, the clump of cells that implants itself in the womb on the seventh day of its existence becomes, within three to four weeks, a well-structured embryo that already contains all the body organs.
“The drama is in the first month, the remaining eight months of pregnancy are mainly lots of growth,” Hanna says. “But that first month is still largely a black box. Our stem cell–derived human embryo model offers an ethical and accessible way of peering into this box. It closely mimics the development of a real human embryo, particularly the emergence of its exquisitely fine architecture.”
Letting the embryo model say ‘Go!’
Hanna’s team built on their previous experience in creating synthetic stem cell–based models of mouse embryos. As in that research, the scientists made no use of fertilized eggs or a womb. Rather, they started out with human cells known as pluripotent stem cells, which have the potential to differentiate into many, though not all, cell types. Some were derived from adult skin cells that had been reverted to “stemness.” Others were the progeny of human stem cell lines that had been cultured for years in the lab.
The researchers then used Hanna’s recently developed method to reprogram pluripotent stem cells so as to turn the clock further back: to revert these cells to an even earlier state—known as the naïve state—in which they are capable of becoming anything, that is, specializing into any type of cell.
This stage corresponds to day 7 of the natural human embryo, around the time it implants itself in the womb. Hanna’s team had in fact been the first to start describing methods to generate human naïve stem cells, back in 2013; they continued to improve these methods, which stand at the heart of the current project, over the years.
[embedded content]Video of a stem cell–derived human embryo model at a developmental stage equivalent to that of a human embryo at day 14. It shows the hormone used in pregnancy tests (green) and the outer layer that will become the placenta (pink), including characteristic cavities, called lacunae. During normal pregnancy, the lacunae allow the exchange of nutrients and waste products between the maternal blood and the fetus. Credit: Weizmann Institute of Science
The scientists divided the cells into three groups. The cells intended to develop into the embryo were left as is. The cells in each of the other groups were treated only with chemicals, without any need for genetic modification, so as to turn on certain genes, which was intended to cause these cells to differentiate toward one of three tissue types needed to sustain the embryo: placenta, yolk sac or the extraembryonic mesoderm membrane that ultimately creates the chorionic sac.
Soon after being mixed together under optimized, specifically developed conditions, the cells formed clumps, about 1 percent of which self-organized into complete embryo-like structures. “An embryo is self-driven by definition; we don’t need to tell it what to do—we must only unleash its internally encoded potential,” Hanna says. “It’s critical to mix in the right kinds of cells at the beginning, which can only be derived from naïve stem cells that have no developmental restrictions. Once you do that, the embryo-like model itself says, ‘Go!'”
The stem cell–based embryo-like structures (termed SEMs) developed normally outside the womb for 8 days, reaching a developmental stage equivalent to day 14 in human embryonic development. That’s the point at which natural embryos acquire the internal structures that enable them to proceed to the next stage: developing the progenitors of body organs.
Complete human embryo models match classic diagrams in terms of structure and cell identity
When the researchers compared the inner organization of their stem cell–derived embryo models with illustrations and microscopic anatomy sections in classical embryology atlases from the 1960s, they found an uncanny structural resemblance between the models and the natural human embryos at the corresponding stage. Every compartment and supporting structure was not only there, but in the right place, size and shape. Even the cells that make the hormone used in pregnancy testing were there and active: When the scientists applied secretions from these cells to a commercial pregnancy test, it came out positive.
This implied that their models faithfully emulated the process by which an early embryo gains all the structures it needs for beginning its transformation into a fetus. “Many failures of pregnancy occur in the first few weeks, often before the woman even knows she’s pregnant,” Hanna says. “That’s also when many birth defects originate, even though they tend to be discovered much later. Our models can be used to reveal the biochemical and mechanical signals that ensure proper development at this early stage, and the ways in which that development can go wrong.”
[embedded content]A video presenting the characteristic structure of the yolk sac (yellow) in a stem cell–derived human embryo model at a developmental stage equivalent to that of a human embryo at day 12. It shows the sac’s upper and lower parts, which have different shapes and functions, and a cavity between the two. Credit: Weizmann Institute of Science
In fact, the study has already produced a finding that may open a new direction of research into early pregnancy failure. The researchers discovered that if the embryo is not enveloped by placenta-forming cells in the right manner at day 3 of the protocol (corresponding to day 10 in natural embryonic development), its internal structures, such as the yolk sac, fail to properly develop.
“An embryo is not static. It must have the right cells in the right organization, and it must be able to progress—it’s about being and becoming,” Hanna says. “Our complete embryo models will help researchers address the most basic questions about what determines its proper growth.”
This ethical approach to unlocking the mysteries of the very first stages of embryonic development could open numerous research paths. It might help reveal the causes of many birth defects and types of infertility. It could also lead to new technologies for growing transplant tissues and organs. And it could offer a way around experiments that cannot be performed on live embryos—for example, determining the effects of exposure to drugs or other substances on fetal development.
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TEL AVIV, Israel (AP) — A rare Bronze-Era jar accidentally smashed by a 4-year-old visiting a museum was back on display Wednesday after restoration experts were able to carefully piece the artifact back together.
Last month, a family from northern Israel was visiting the museum when their youngest son tipped over the jar, which smashed into pieces.
Alex Geller, the boy’s father, said his son — the youngest of three — is exceptionally curious, and that the moment he heard the crash, “please let that not be my child” was the first thought that raced through his head.
The jar has been on display at the Hecht Museum in Haifa for 35 years. It was one of the only containers of its size and from that period still complete when it was discovered.
The Bronze Age jar is one of many artifacts exhibited out in the open, part of the Hecht Museum’s vision of letting visitors explore history without glass barriers, said Inbal Rivlin, the director of the museum, which is associated with Haifa University in northern Israel.
It was likely used to hold wine or oil, and dates back to between 2200 and 1500 B.C.
Rivlin and the museum decided to turn the moment, which captured international attention, into a teaching moment, inviting the Geller family back for a special visit and hands-on activity to illustrate the restoration process.
Rivlin added that the incident provided a welcome distraction from the ongoing war in Gaza. “Well, he’s just a kid. So I think that somehow it touches the heart of the people in Israel and around the world,“ said Rivlin.
Roee Shafir, a restoration expert at the museum, said the repairs would be fairly simple, as the pieces were from a single, complete jar. Archaeologists often face the more daunting task of sifting through piles of shards from multiple objects and trying to piece them together.
Experts used 3D technology, hi-resolution videos, and special glue to painstakingly reconstruct the large jar.
Less than two weeks after it broke, the jar went back on display at the museum. The gluing process left small hairline cracks, and a few pieces are missing, but the jar’s impressive size remains.
The only noticeable difference in the exhibit was a new sign reading “please don’t touch.”
VICTORIA – The British Columbia government is partnering with a bear welfare group to reduce the number of bears being euthanized in the province.
Nicholas Scapillati, executive director of Grizzly Bear Foundation, said Monday that it comes after months-long discussions with the province on how to protect bears, with the goal to give the animals a “better and second chance at life in the wild.”
Scapillati said what’s exciting about the project is that the government is open to working with outside experts and the public.
“So, they’ll be working through Indigenous knowledge and scientific understanding, bringing in the latest techniques and training expertise from leading experts,” he said in an interview.
B.C. government data show conservation officers destroyed 603 black bears and 23 grizzly bears in 2023, while 154 black bears were killed by officers in the first six months of this year.
Scapillati said the group will publish a report with recommendations by next spring, while an independent oversight committee will be set up to review all bear encounters with conservation officers to provide advice to the government.
Environment Minister George Heyman said in a statement that they are looking for new ways to ensure conservation officers “have the trust of the communities they serve,” and the panel will make recommendations to enhance officer training and improve policies.
Lesley Fox, with the wildlife protection group The Fur-Bearers, said they’ve been calling for such a committee for decades.
“This move demonstrates the government is listening,” said Fox. “I suspect, because of the impending election, their listening skills are potentially a little sharper than they normally are.”
Fox said the partnership came from “a place of long frustration” as provincial conservation officers kill more than 500 black bears every year on average, and the public is “no longer tolerating this kind of approach.”
“I think that the conservation officer service and the B.C. government are aware they need to change, and certainly the public has been asking for it,” said Fox.
Fox said there’s a lot of optimism about the new partnership, but, as with any government, there will likely be a lot of red tape to get through.
“I think speed is going to be important, whether or not the committee has the ability to make change and make change relatively quickly without having to study an issue to death, ” said Fox.
This report by The Canadian Press was first published Sept. 9, 2024.
The European Space Agency is fast-tracking a new mission called Ramses, which will fly to near-Earth asteroid 99942 Apophis and join the space rock in 2029 when it comes very close to our planet — closer even than the region where geosynchronous satellites sit.
Ramses is short for Rapid Apophis Mission for Space Safety and, as its name suggests, is the next phase in humanity’s efforts to learn more about near-Earth asteroids (NEOs) and how we might deflect them should one ever be discovered on a collision course with planet Earth.
In order to launch in time to rendezvous with Apophis in February 2029, scientists at the European Space Agency have been given permission to start planning Ramses even before the multinational space agency officially adopts the mission. The sanctioning and appropriation of funding for the Ramses mission will hopefully take place at ESA’s Ministerial Council meeting (involving representatives from each of ESA’s member states) in November of 2025. To arrive at Apophis in February 2029, launch would have to take place in April 2028, the agency says.
This is a big deal because large asteroids don’t come this close to Earth very often. It is thus scientifically precious that, on April 13, 2029, Apophis will pass within 19,794 miles (31,860 kilometers) of Earth. For comparison, geosynchronous orbit is 22,236 miles (35,786 km) above Earth’s surface. Such close fly-bys by asteroids hundreds of meters across (Apophis is about 1,230 feet, or 375 meters, across) only occur on average once every 5,000 to 10,000 years. Miss this one, and we’ve got a long time to wait for the next.
When Apophis was discovered in 2004, it was for a short time the most dangerous asteroid known, being classified as having the potential to impact with Earth possibly in 2029, 2036, or 2068. Should an asteroid of its size strike Earth, it could gouge out a crater several kilometers across and devastate a country with shock waves, flash heating and earth tremors. If it crashed down in the ocean, it could send a towering tsunami to devastate coastlines in multiple countries.
Over time, as our knowledge of Apophis’ orbit became more refined, however, the risk of impact greatly went down. Radar observations of the asteroid in March of 2021 reduced the uncertainty in Apophis’ orbit from hundreds of kilometers to just a few kilometers, finally removing any lingering worries about an impact — at least for the next 100 years. (Beyond 100 years, asteroid orbits can become too unpredictable to plot with any accuracy, but there’s currently no suggestion that an impact will occur after 100 years.) So, Earth is expected to be perfectly safe in 2029 when Apophis comes through. Still, scientists want to see how Apophis responds by coming so close to Earth and entering our planet’s gravitational field.
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“There is still so much we have yet to learn about asteroids but, until now, we have had to travel deep into the solar system to study them and perform experiments ourselves to interact with their surface,” said Patrick Michel, who is the Director of Research at CNRS at Observatoire de la Côte d’Azur in Nice, France, in a statement. “Nature is bringing one to us and conducting the experiment itself. All we need to do is watch as Apophis is stretched and squeezed by strong tidal forces that may trigger landslides and other disturbances and reveal new material from beneath the surface.”
The Goldstone radar’s imagery of asteroid 99942 Apophis as it made its closest approach to Earth, in March 2021. (Image credit: NASA/JPL–Caltech/NSF/AUI/GBO)
By arriving at Apophis before the asteroid’s close encounter with Earth, and sticking with it throughout the flyby and beyond, Ramses will be in prime position to conduct before-and-after surveys to see how Apophis reacts to Earth. By looking for disturbances Earth’s gravitational tidal forces trigger on the asteroid’s surface, Ramses will be able to learn about Apophis’ internal structure, density, porosity and composition, all of which are characteristics that we would need to first understand before considering how best to deflect a similar asteroid were one ever found to be on a collision course with our world.
Besides assisting in protecting Earth, learning about Apophis will give scientists further insights into how similar asteroids formed in the early solar system, and, in the process, how planets (including Earth) formed out of the same material.
One way we already know Earth will affect Apophis is by changing its orbit. Currently, Apophis is categorized as an Aten-type asteroid, which is what we call the class of near-Earth objects that have a shorter orbit around the sun than Earth does. Apophis currently gets as far as 0.92 astronomical units (137.6 million km, or 85.5 million miles) from the sun. However, our planet will give Apophis a gravitational nudge that will enlarge its orbit to 1.1 astronomical units (164.6 million km, or 102 million miles), such that its orbital period becomes longer than Earth’s.
It will then be classed as an Apollo-type asteroid.
Ramses won’t be alone in tracking Apophis. NASA has repurposed their OSIRIS-REx mission, which returned a sample from another near-Earth asteroid, 101955 Bennu, in 2023. However, the spacecraft, renamed OSIRIS-APEX (Apophis Explorer), won’t arrive at the asteroid until April 23, 2029, ten days after the close encounter with Earth. OSIRIS-APEX will initially perform a flyby of Apophis at a distance of about 2,500 miles (4,000 km) from the object, then return in June that year to settle into orbit around Apophis for an 18-month mission.
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Furthermore, the European Space Agency still plans on launching its Hera spacecraft in October 2024 to follow-up on the DART mission to the double asteroid Didymos and Dimorphos. DART impacted the latter in a test of kinetic impactor capabilities for potentially changing a hazardous asteroid’s orbit around our planet. Hera will survey the binary asteroid system and observe the crater made by DART’s sacrifice to gain a better understanding of Dimorphos’ structure and composition post-impact, so that we can place the results in context.
The more near-Earth asteroids like Dimorphos and Apophis that we study, the greater that context becomes. Perhaps, one day, the understanding that we have gained from these missions will indeed save our planet.
