The multi-centre team is led by the Wellcome Sanger Institute and the National Heart and Lung Institute at Imperial College London, and has also presented a new drug-repurposing computational tool called Drug2cell, which can provide insights into the effects of drugs on heart rate.

This study is part of the international Human Cell Atlas* (HCA) initiative, which is mapping every cell type in the human body, to transform our understanding of health and disease, and will form the foundation for a fully integrated HCA Human Heart Cell Atlas.

Charting eight regions of the human heart, the work describes 75 different cell states including the cells of the cardiac conduction system — the group of cells responsible for the heartbeat — not understood at such a detailed level (1) in humans before. The human cardiac conduction system, the heart’s ‘wiring’, sends electrical impulses from the top to the bottom of the heart and coordinates the heartbeat.

By using spatial transcriptomics, which gives a “map” of where cells sit within a tissue, researchers were also able to understand how these cells communicate with each other for the first time. This map acts as a molecular guidebook, showing what healthy cells look like, and providing a crucial reference to understand what goes wrong in disease. The findings will help understand diseases such as those affecting the heart rhythm.

The assembly of a Human Heart Cell Atlas is key given that cardiovascular diseases are the leading cause of death globally. Around 20,000 electronic pacemakers are implanted each year in the UK for these disorders (2). These can be ineffective and are prone to complications and side-effects (3). Understanding the biology of the cells of the conduction system and how they differ from muscle cells paves the way to therapies to boost cardiac health and develop targeted treatments for arrhythmias.

The team also presents a new computational tool called Drug2cell. The tool can predict drug targets as well as drug side effects. It leverages single-cell profiles and the 19 million drug-target interactions in the EMBL-EBI ChEMBL database.

Unexpectedly, this tool identified that pacemaker cells express the target of certain medications, such as GLP1 drugs, which are used for diabetes and weight loss and are known to increase the heart rate as a side-effect, the mechanism of which was unclear. This study suggests that the increase in heart rate might be partly due to a direct action of these drugs on pacemaker cells, a finding the team also showed in an experimental stem cell model of pacemaker cells.

Dr James Cranley, joint first author, a cardiologist specialising in heart rhythm disorders and PhD student at the Wellcome Sanger Institute, said: “The cardiac conduction system is critical for the regular and coordinated beating of our hearts, yet the cells which make it up are poorly understood. This study sheds new light by defining the profiles of these cells, as well as the multicellular niches they inhabit. This deeper understanding opens the door to better, targeted anti-arrhythmic therapies in the future.”

Dr Kazumasa Kanemaru, joint first author and Postdoctoral Fellow in the Gene Expression Genomics team at the Wellcome Sanger Institute, said: “The mechanism of activating and suppressing pacemaker cell genes is not clear, especially in humans. This is important for improving cell therapy to facilitate the production of pacemaker cells or to prevent the excessive spontaneous firing of cells. By understanding these cells at an individual genetic level, we can potentially develop new ways to improve heart treatments.”

The study unearthed an unexpected discovery: a close relationship between conduction system cells and glial cells. Glial cells are part of the nervous system and are traditionally found in the brain. They have been explored very little in the heart. This research suggests that glial cells are in physical contact with conduction system cells and may play an important supporting role: communicating with the pacemaker cells, guiding nerve endings to them, and supporting their release of glutamate, a neurotransmitter.

Another key finding of the study is an immune structure on the heart’s outer surface. This contains plasma cells, which release antibodies into the space around the heart to prevent infection from the nearby lungs. The researchers also identified a cellular niche enriching for a hormone (4) that could be interpreted as an early warning sign of heart failure.

Dr Michela Noseda, senior Lecturer in Cardiac Molecular Pathology at the National Heart and Lung Institute, Imperial College London, a Coordinator of the Human Cell Atlas Heart BioNetwork and a lead author, said: “We often don’t fully know what impact a new treatment will have on the heart and its electrical impulses — this can mean a drug is withdrawn or fails to make it to the market. Our team developed the Drug2cell platform to improve how we evaluate new treatments and how they can affect our hearts, and potentially other tissues too. This could provide us with an invaluable tool to identify new drugs which target specific cells, as well as help to predict any potential side-effects early on in drug development.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, which part-funded the research with the German Centre for Cardiovascular Research (DZHK), said: “Using cutting-edge technologies, this research provides further intricate detail about the cells that make up specialised regions of the human heart and how those cells communicate with each other. The new findings on the heart’s electrical conduction system and its regulation are likely to open up new approaches to preventing and treating rhythm disturbances that can impair the heart’s function and may even become life-threatening.”

“International collaboration is key to scientific progress. This impactful study and other discoveries from the broader Human Cell Atlas initiative are excellent examples of what can be achieved when the international research community works together across borders. Our combined efforts can ultimately produce better outcomes for patients worldwide.”

Dr Sarah Teichmann, a senior author of the study from the Wellcome Sanger Institute and co-chair of the Human Cell Atlas Organising Committee, said: “This Heart Cell Atlas reveals cardiac microanatomy in unprecedented detail, including the cardiac conduction system that enables each heartbeat, and is a valuable reference for studying heart disease and designing potential therapeutics. An important contribution to the global Human Cell Atlas initiative, which is mapping every cell type in the body to understand health and disease, it will form the foundation for a fully integrated HCA Human Heart Cell Atlas. In addition, our suite of computational methods will help identify possibilities for repurposing existing drugs to treat diseases in other tissues.”

More information can be found at https://www.humancellatlas.org/

“We found microplastics in every lake we sampled,” said Ted Harris, associate research professor for the Kansas Biological Survey & Center for Ecological Research at the University of Kansas.

“Some of these lakes you think of as clear, beautiful vacation spots. But we discovered such places to be perfect examples of the link between plastics and humans.”

Harris is one of 79 researchers belonging to the international Global Lake Ecological Observatory Network (GLEON), which examines processes and phenomena occurring in freshwater environments. Their new paper, titled “Plastic debris in lakes and reservoirs,” reveals that concentrations of plastic found in freshwater environments are actually higher than those found in so-called “garbage patches” in the ocean. The article is published in Nature.

For his role, Harris teamed with Rebecca Kessler, his former student and recent KU graduate, to test two Kansas lakes (Clinton and Perry) and the Cross Reservoir at the KU Field Station.

“That entailed us going out, tolling a net with tiny little holes in it, dragging it for about two minutes, then collecting those samples of microplastics and sending them off to (the lead researchers),” Kessler said.

The research project was designed and coordinated by the Inland Water Ecology and Management research group of the University of Milano-Bicocca, Italy (headed by Barbara Leoni and Veronica Nava). The team sampled surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes. It detected plastic debris in all studied lakes and reservoirs.

“This paper essentially shows the more humans, the more plastics,” Harris said. “Places like Clinton Lake are relatively low in microplastics because — while there are many animals and trees — there aren’t a lot of humans, relative to somewhere like Lake Tahoe where people are living all around it. Some of these lakes are seemingly pristine and beautiful, yet that’s where the microplastics come from.”

Harris said that many of the plastics are from something as outwardly innocuous as T-shirts.

“The simple act of people getting in swimming and having clothing that has microplastic fibers in it leads to microplastics getting everywhere,” he said.

The GLEON study cites two types of water bodies studied that are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas; and those with elevated deposition areas, long water retention times and high levels of anthropogenic influence.

“When we started the study, I didn’t know a lot about microplastics versus large plastics,” Harris said.

“When this paper says ‘concentrations as much or worse than the garbage patch,’ you always think of the big bottles and stuff, but you’re not thinking of all that smaller stuff. You don’t see a huge garbage patch in Lake Tahoe, yet it’s one of the most impacted lakes when it comes to microplastics. Those are plastics you can’t really see with the naked eye, and then you get underneath a scope at 40,000x, and you see these little jagged pieces and other particles that are the same size as algae or even smaller.”

Part of Harris and Kessler’s enthusiasm for taking part in this project was to highlight a region of the U.S. that is often overlooked.

“In this study, there’s one dot in the middle of the country, and that’s our sample,” he said. “In Iowa, Missouri and Colorado, there’s this huge swath of area that has water bodies, but we often don’t get them into those massive global studies. So it was really important for me to put Kansas on the map to see and contextualize what these differences are in our lakes.”

Harris has worked at KU since 2013, where his research focuses on aquatic ecology. Kessler graduated KU in 2022 with a degree in ecology, evolutionary & organismal biology.

“The biggest takeaway from our study is that microplastics can be found in all lakes,” Kessler said. “Obviously, there are different concentrations. But they are literally everywhere. And the biggest contributing factor to these microplastics is human interaction with the lakes.”

Not only does this improve the material’s ability to conduct electricity with no loss, they said, but it also allows them to discover its true nature and properties, both in and out of the superconducting state, for the first time.

Their first look at a superconducting nickel oxide, or nickelate, that does not have defects revealed that it is more like the cuprates – which hold the world’s high-temperature record for unconventional superconductivity at normal pressures — than previously thought. For instance, when the nickelate is tweaked to optimize its superconductivity and then heated above its superconducting temperature, its resistance to the flow of electric current increases in a linear fashion, just as in cuprates.

Those striking similarities, they said, may mean these two very different materials achieve superconductivity in much the same way.

It’s the latest step in a 35-year quest to develop superconductors that can operate at close to room temperature, which would revolutionize electronics, transportation, power transmission and other technologies by allowing them to operate without energy-wasting electrical resistance.

The research team, led by Harold Hwang, director of the Stanford Institute for Materials and Energy Sciences (SIMES) at SLAC, described their work today in the journal Nature.

“Nickelate films are really unstable, and until now our efforts to stabilize them on top of other materials have produced defects that are like speed bumps for electrons,” said Kyuho Lee, a SIMES postdoctoral researcher who contributed to the discovery of superconductivity in nickelates four years ago and has been working on them ever since.

“These quality issues have led to many debates and open questions about nickelate properties, with research groups reporting widely varying results,” Lee said. “So eliminating the defects is a significant breakthrough. It means we can finally address the underlying physics behind these materials and behind unconventional superconductivity in general.”

Jenga chemistry and a just-right fit

The defects, which are a bit like misaligned zipper teeth, arise from the same innovative process that allowed Hwang’s team to create and stabilize a nickelate film in the first place.

They started by making a common material known as perovskite. They “doped” it to change its electrical conductivity, then exposed it to a chemical that deftly removed layers of oxygen atoms from its molecular structure, much like removing a stick from a tower of Jenga blocks. With the oxygen layers gone, the film settled into a new structure — known as an infinite-layer nickelate -that can host superconductivity.

The atomic latticework of this new structure occupied a slightly bigger surface area than the original. With this in mind, they had built the film on a foundation, or substrate, that would be a good fit for the finished, spread-out product, Lee said.

But it didn’t match the atomic lattice of the starting material, which developed defects as it tried to fit comfortably onto the substrate — and those imperfections carried through to the finished nickelate.

Hwang said it’s as if two friends of different sizes had to share a coat. If the coat fit the smaller friend perfectly, the larger one would have a hard time zipping it up. If it fit the larger friend perfectly, it would hang like a tent on the smaller one and let the cold in. An in-between size might not be the best fit for either of them, but it’s close enough to keep them both warm and happy.

That’s the solution Lee and his colleagues pursued.

In a series of meticulous experiments, they used a substrate that was like the in-between coat. The atomic structure of its surface was a close enough fit for both the starting and ending materials that the finished nickelate came out defect-free. Lee said the team is already starting to see some interesting physics in the nickelate now that the system is much cleaner.

“What this means,” Hwang said, “is that we are getting closer and closer to measuring the intrinsic properties of these materials. And by sharing the details of how to make defect-free nickelates, we hope to benefit the field as a whole.”

Researchers from Cornell University contributed to this work, which was funded by the DOE Office of Science and the Gordon and Betty Moore Foundation’s Emergent Phenomena in Quantum Systems Initiative.