The most detailed and comprehensive human Heart Cell Atlas could help clinicians to develop new ways to improve heart treatments, researchers said last night.
The atlas, published by a multi-centre team led by the Wellcome Sanger Institute and the National Heart and Lung Institute at Imperial College London, UK, also examines the potential for a new drug-repurposing computational tool that can provide insights into the effects of drugs on heart rate.
The study, part of the international Human Cell Atlas (HCA) initiative, focuses on eight regions of the human heart and describes 75 different cell states, including the cells of the cardiac conduction system, which has never been examined in such detail in humans before.
Writing in Nature, the researchers describe using spatial transcriptomics to provide a “map” of where cells sit within a tissue, which enabled them to understand how the cells communicate with each other for the first time.
The team also introduce Drug2cell, a new computational tool that can predict drug targets as well as drug side effects.
They found the tool identified that pacemaker cells express the target of certain medications, such as GLP1 drugs, used for diabetes and weight loss and are known to increase the heart rate.
This study suggested the increase in heart rate might be due in part to a direct action of these drugs on pacemaker cells.
Joint first author Dr James Cranley, from 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 from the Wellcome Sanger Institute, added: “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 also discovered a close relationship between conduction system cells and glial cells. The researchers believe glial cells are in physical contact with conduction system cells and may help to communicate with the pacemaker cells, guiding nerve endings to them and supporting their release of glutamate.
Dr Michela Noseda, senior lecturer in cardiac molecular pathology at the National Heart and Lung Institute, Imperial College London, 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.”
Senior study author Dr Sarah Teichmann, from the Wellcome Sanger Institute said the atlas was a valuable reference for studying heart disease and reveals cardiac microanatomy in unprecedented detail.
Kanemaru K, Cranley J, Muraro D et al. Spatially resolved multiomics of human cardiac niches. Nature 12 July 2023; doi: 10.1038/s41586-023-06311-1
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