Connect with us

TOP SCEINCE

Epigenetic changes reprogram astrocytes into brain stem cells

Published

on

Epigenetic changes reprogram astrocytes into brain stem cells


Resting brain stem cells hardly differ from normal astrocytes, which support the nerve cells in the brain. How can almost identical cells perform such different functions? The key lies in the methylation of their genetic material, which endowes these special astrocytes with stem cell properties. Scientists from the German Cancer Research Center (DKFZ) and Heidelberg University have published their findings in the journal Nature. In mice, the researchers showed that experimentally induced lack of blood supply in the brain epigenetically reprograms astrocytes into brain stem cells, which in turn can give rise to nerve progenitor cells. This discovery shows that astrocytes could potentially be used in regenerative medicine to replace damaged nerve cells.

Many different types of cells work together in the brain. In humans, nerve cells (neurons) make up less than half of the cells. The rest are called “glia.” The most common glial cells are astrocytes. They supply the neurons with nutrients, form part of the blood-brain barrier, regulate the synapses and support the immune cells.

However, a small proportion of astrocytes are able to produce nerve cells and other types of brain cells. These special astrocytes are therefore also known as brain stem cells. Brain stem cells and ordinary astrocytes hardly differ in their gene expression, i.e. in the activity of their genes. “How they can perform such different functions and what makes up the stem cell properties was previously completely unclear,” explains Ana Martin-Villalba, stem cell researcher at the DKFZ.

Methylation is the key

To solve this puzzle, the teams led by Martin-Villalba and Simon Anders (University of Heidelberg) isolated both ordinary astrocytes and brain stem cells from one of the regions of the brain where young neurons still develop in adult mice, the “ventricular-subventricular zone” (vSVZ). The researchers analyzed gene expression at the level of individual cells using mRNA sequencing as well as the patterns of methylation (“methylome”) in the entire genome. They used a specially developed tool to analyze the methylation data*.

DNA methylation refers to chemical “markers” with which the cell can switch off unused parts of its DNA. Methylation is therefore crucial for the identity of the cells.

During this study, the stem cell experts noticed that brain stem cells have a special DNA methylation pattern that distinguishes them from other astrocytes. “Unlike normal astrocytes, certain genes are demethylated in brain stem cells that are otherwise only used by nerve precursor cells. This allows the brain stem cells to activate these genes in order to produce nerve cells themselves,” explains Lukas Kremer, first author of the current publication. Co-first author Santiago Cerrizuela adds: “This pathway is denied to ordinary astrocytes, as the required genes are blocked by DNA methylation.”

Lack of blood supply triggers reprogramming of astrocytes to stem cells and increases new nerve formation

Could methylation also be used to convert astrocytes into brain stem cells in other regions of the brain, outside the vSVZ? “This would be an important step for regenerative medicine to repair damaged areas of the brain,” says Ana Martin-Villalba.

Earlier studies had already shown that a lack of blood supply, such as occurs in brain injuries or stroke, increases the number of newborn nerve cells. Do altered methylation profiles play a role in this process?

To investigate this, the researchers interrupted the blood supply to the brain of mice for a short time. As a result, astrocytes with the typical stem cell methylation profile could be detected even outside the vSVZ, as well as an increased number of nerve progenitor cells.

“Our theory is that normal astrocytes in the healthy brain do not form nerve cells because their methylation pattern prevents them from doing so,” explains study head Martin-Villalba. “Techniques to specifically alter the methylation profile could represent a new therapeutic approach to generate new neurons and treat nerve diseases.”

“The lack of blood supply apparently causes astrocytes in certain areas of the brain to redistribute the methyl marks on their DNA in such a way that their stem cell program becomes accessible. The reprogrammed cells then begin to divide and form precursors for new neurons,” summarizes Simon Anders and adds: “If we understand these processes better, we may be able to specifically stimulate the formation of new neurons in the future. For example, after a stroke, we could strengthen the brain’s self-healing powers, so that the damage can be repaired.”

Why studies on mice are necessary for this research

Strokes or accidents can lead to damage to the brain that is generally irreparable at present and often has dramatic consequences for those affected. As of today, there is no way to replace lost nerve cells. The aim of this work is to find ways to stimulate the regeneration of nerves in the adult brain.

This requires a profound understanding of how and under what circumstances brain stem cells can be induced to provide a supply of young nerve cells. To do this, the researchers need to study developmental processes that only take place in the brains of highly developed mammals. Epigenetic reprogramming cannot be observed in living animals using imaging techniques, but requires studies at the level of individual cells. The investigations cannot be carried out on cells from the culture dish, as the methylation profile of the astrocytes changes as soon as they are taken into culture, so that the epigenetic reprogramming can no longer be traced.



Source link

Continue Reading
Click to comment

Leave a Reply

TOP SCEINCE

Early dark energy could resolve cosmology’s two biggest puzzles

Published

on

By

Epigenetic changes reprogram astrocytes into brain stem cells


A new study by MIT physicists proposes that a mysterious force known as early dark energy could solve two of the biggest puzzles in cosmology and fill in some major gaps in our understanding of how the early universe evolved.

One puzzle in question is the “Hubble tension,” which refers to a mismatch in measurements of how fast the universe is expanding. The other involves observations of numerous early, bright galaxies that existed at a time when the early universe should have been much less populated.

Now, the MIT team has found that both puzzles could be resolved if the early universe had one extra, fleeting ingredient: early dark energy. Dark energy is an unknown form of energy that physicists suspect is driving the expansion of the universe today. Early dark energy is a similar, hypothetical phenomenon that may have made only a brief appearance, influencing the expansion of the universe in its first moments before disappearing entirely.

Some physicists have suspected that early dark energy could be the key to solving the Hubble tension, as the mysterious force could accelerate the early expansion of the universe by an amount that would resolve the measurement mismatch.

The MIT researchers have now found that early dark energy could also explain the baffling number of bright galaxies that astronomers have observed in the early universe. In their new study, reported in the Monthly Notices of the Royal Astronomical Society, the team modeled the formation of galaxies in the universe’s first few hundred million years. When they incorporated a dark energy component only in that earliest sliver of time, they found the number of galaxies that arose from the primordial environment bloomed to fit astronomers’ observations.

You have these two looming open-ended puzzles,” says study co-author Rohan Naidu, a postdoc in MIT’s Kavli Institute for Astrophysics and Space Research. “We find that in fact, early dark energy is a very elegant and sparse solution to two of the most pressing problems in cosmology.”

The study’s co-authors include lead author and Kavli postdoc Xuejian (Jacob) Shen, and MIT professor of physics Mark Vogelsberger, along with Michael Boylan-Kolchin at the University of Texas at Austin, and Sandro Tacchella at the University of Cambridge.

Big city lights

Based on standard cosmological and galaxy formation models, the universe should have taken its time spinning up the first galaxies. It would have taken billions of years for primordial gas to coalesce into galaxies as large and bright as the Milky Way.

But in 2023, NASA’s James Webb Space Telescope (JWST) made a startling observation. With an ability to peer farther back in time than any observatory to date, the telescope uncovered a surprising number of bright galaxies as large as the modern Milky Way within the first 500 million years, when the universe was just 3 percent of its current age.

“The bright galaxies that JWST saw would be like seeing a clustering of lights around big cities, whereas theory predicts something like the light around more rural settings like Yellowstone National Park,” Shen says. “And we don’t expect that clustering of light so early on.”

For physicists, the observations imply that there is either something fundamentally wrong with the physics underlying the models or a missing ingredient in the early universe that scientists have not accounted for. The MIT team explored the possibility of the latter, and whether the missing ingredient might be early dark energy.

Physicists have proposed that early dark energy is a sort of antigravitational force that is turned on only at very early times. This force would counteract gravity’s inward pull and accelerate the early expansion of the universe, in a way that would resolve the mismatch in measurements. Early dark energy, therefore, is considered the most likely solution to the Hubble tension.

Galaxy skeleton

The MIT team explored whether early dark energy could also be the key to explaining the unexpected population of large, bright galaxies detected by JWST. In their new study, the physicists considered how early dark energy might affect the early structure of the universe that gave rise to the first galaxies. They focused on the formation of dark matter halos — regions of space where gravity happens to be stronger, and where matter begins to accumulate.

“We believe that dark matter halos are the invisible skeleton of the universe,” Shen explains. “Dark matter structures form first, and then galaxies form within these structures. So, we expect the number of bright galaxies should be proportional to the number of big dark matter halos.”

The team developed an empirical framework for early galaxy formation, which predicts the number, luminosity, and size of galaxies that should form in the early universe, given some measures of “cosmological parameters.” Cosmological parameters are the basic ingredients, or mathematical terms, that describe the evolution of the universe.

Physicists have determined that there are at least six main cosmological parameters, one of which is the Hubble constant — a term that describes the universe’s rate of expansion. Other parameters describe density fluctuations in the primordial soup, immediately after the Big Bang, from which dark matter halos eventually form.

The MIT team reasoned that if early dark energy affects the universe’s early expansion rate, in a way that resolves the Hubble tension, then it could affect the balance of the other cosmological parameters, in a way that might increase the number of bright galaxies that appear at early times. To test their theory, they incorporated a model of early dark energy (the same one that happens to resolve the Hubble tension) into an empirical galaxy formation framework to see how the earliest dark matter structures evolve and give rise to the first galaxies.

“What we show is, the skeletal structure of the early universe is altered in a subtle way where the amplitude of fluctuations goes up, and you get bigger halos, and brighter galaxies that are in place at earlier times, more so than in our more vanilla models,” Naidu says. “It means things were more abundant, and more clustered in the early universe.”

“A priori, I would not have expected the abundance of JWST’s early bright galaxies to have anything to do with early dark energy, but their observation that EDE pushes cosmological parameters in a direction that boosts the early-galaxy abundance is interesting,” says Marc Kamionkowski, professor of theoretical physics at Johns Hopkins University, who was not involved with the study. “I think more work will need to be done to establish a link between early galaxies and EDE, but regardless of how things turn out, it’s a clever — and hopefully ultimately fruitful — thing to try.”

We demonstrated the potential of early dark energy as a unified solution to the two major issues faced by cosmology. This might be an evidence for its existence if the observational findings of JWST get further consolidated,” Vogelsberger concludes. “In the future, we can incorporate this into large cosmological simulations to see what detailed predictions we get.”

This research was supported, in part, by NASA and the National Science Foundation.



Source link

Continue Reading

TOP SCEINCE

Plant-derived secondary organic aerosols can act as mediators of plant-plant interactions

Published

on

By

Epigenetic changes reprogram astrocytes into brain stem cells


A new study published in Science reveals that plant-derived secondary organic aerosols (SOAs) can act as mediators of plant-plant interactions. This research was conducted through the cooperation of chemical ecologists, plant ecophysiologists and atmospheric physicists at the University of Eastern Finland.

It is well known that plants release volatile organic compounds (VOCs) into the atmosphere when damaged by herbivores. These VOCs play a crucial role in plant-plant interactions, whereby undamaged plants may detect warning signals from their damaged neighbours and prepare their defences. “Reactive plant VOCs undergo oxidative chemical reactions, resulting in the formation of secondary organic aerosols (SOAs). We wondered whether the ecological functions mediated by VOCs persist after they are oxidated to form SOAs,” said Dr. Hao Yu, formerly a PhD student at UEF, but now at the University of Bern.

The study showed that Scots pine seedlings, when damaged by large pine weevils, release VOCs that activate defences in nearby plants of the same species. Interestingly, the biological activity persisted after VOCs were oxidized to form SOAs. The results indicated that the elemental composition and quantity of SOAs likely determines their biological functions.

“A key novelty of the study is the finding that plants adopt subtly different defence strategies when receiving signals as VOCs or as SOAs, yet they exhibit similar degrees of resistance to herbivore feeding,” said Professor James Blande, head of the Environmental Ecology Research Group. This observation opens up the possibility that plants have sophisticated sensing systems that enable them to tailor their defences to information derived from different types of chemical cue.

“Considering the formation rate of SOAs from their precursor VOCs, their longer lifetime compared to VOCs, and the atmospheric air mass transport, we expect that the ecologically effective distance for interactions mediated by SOAs is longer than that for plant interactions mediated by VOCs,” said Professor Annele Virtanen, head of the Aerosol Physics Research Group. This could be interpreted as plants being able to detect cues representing close versus distant threats from herbivores.

The study is expected to open up a whole new complex research area to environmental ecologists and their collaborators, which could lead to new insights on the chemical cues structuring interactions between plants.



Source link

Continue Reading

TOP SCEINCE

Folded or cut, this lithium-sulfur battery keeps going

Published

on

By

Epigenetic changes reprogram astrocytes into brain stem cells


Most rechargeable batteries that power portable devices, such as toys, handheld vacuums and e-bikes, use lithium-ion technology. But these batteries can have short lifetimes and may catch fire when damaged. To address stability and safety issues, researchers reporting in ACS Energy Letters have designed a lithium-sulfur (Li-S) battery that features an improved iron sulfide cathode. One prototype remains highly stable over 300 charge-discharge cycles, and another provides power even after being folded or cut.

Sulfur has been suggested as a material for lithium-ion batteries because of its low cost and potential to hold more energy than lithium-metal oxides and other materials used in traditional ion-based versions. To make Li-S batteries stable at high temperatures, researchers have previously proposed using a carbonate-based electrolyte to separate the two electrodes (an iron sulfide cathode and a lithium metal-containing anode). However, as the sulfide in the cathode dissolves into the electrolyte, it forms an impenetrable precipitate, causing the cell to quickly lose capacity. Liping Wang and colleagues wondered if they could add a layer between the cathode and electrolyte to reduce this corrosion without reducing functionality and rechargeability.

The team coated iron sulfide cathodes in different polymers and found in initial electrochemical performance tests that polyacrylic acid (PAA) performed best, retaining the electrode’s discharge capacity after 300 charge-discharge cycles. Next, the researchers incorporated a PAA-coated iron sulfide cathode into a prototype battery design, which also included a carbonate-based electrolyte, a lithium metal foil as an ion source, and a graphite-based anode. They produced and then tested both pouch cell and coin cell battery prototypes.

After more than 100 charge-discharge cycles, Wang and colleagues observed no substantial capacity decay in the pouch cell. Additional experiments showed that the pouch cell still worked after being folded and cut in half. The coin cell retained 72% of its capacity after 300 charge-discharge cycles. They next applied the polymer coating to cathodes made from other metals, creating lithium-molybdenum and lithium-vanadium batteries. These cells also had stable capacity over 300 charge-discharge cycles. Overall, the results indicate that coated cathodes could produce not only safer Li-S batteries with long lifespans, but also efficient batteries with other metal sulfides, according to Wang’s team.

The authors acknowledge funding from the National Natural Science Foundation of China; the Natural Science Foundation of Sichuan, China; and the Beijing National Laboratory for Condensed Matter Physics.



Source link

Continue Reading

Trending