Researchers at the University of Notre Dame discovered a new type of cell in the heart that may help regulate heart rate, and may lead to understanding certain types of congenital heart defects and other diseases that affect the heart.

Their findings are published in the journal PLOS Biology in a paper titled “Identification of astroglia-like cardiac nexus glia that are critical regulators of cardiac development and function.”

“Glial cells are essential for functionality of the nervous system,” write he researchers. “Growing evidence underscores the importance of astrocytes; however, analogous astroglia in peripheral organs are poorly understood. Using confocal time-lapse imaging, fate mapping, and mutant genesis in a zebrafish model, we identify a neural crest–derived glial cell, termed nexus glia, which utilizes Meteorin signaling via Jak/Stat3 to drive differentiation and regulate heart rate and rhythm.”

“For me the definition of great science is something that you discover that opens up even more questions, and this, I think, is the definition of that,” explained Cody Smith, the Elizabeth and Michael Gallagher Associate Professor in the Department of Biological Sciences, who is also affiliated with the University’s Center for Stem Cells and Regenerative Medicine. “It’s a discovery that now we have 100 questions we didn’t even know existed, so we’re following up on them to explore this path that has never been studied before.”

The research team made the discovery of the cells in zebrafish hearts, then confirmed their existence in both mouse and human hearts.

“I thought that if we could find a new cellular piece to the cardiovascular puzzle, it could be foundational for future work,” said Nina Kikel-Coury, first author of the paper and a recent graduate of Smith’s lab.

Kikel-Coury was particularly interested in how these cells factored into a group of medical conditions called dysautonomia, which result from faults in the autonomic nervous system. She has one of the conditions, postural orthostatic tachycardia syndrome (POTS), which causes lightheadedness, fainting and a rapid increase in heart rate.

“We don’t completely know the function of these cells, but the concept that if you get rid of them, heart rates increase, could link it to certain disease cases,” Smith said. “I think these glial cells could play a pretty important role in regulating the heart.

“Further, analysis of single-cell sequencing datasets of human and murine hearts across ages reveals astrocyte-like cells, which we confirm through a multispecies approach. We show that cardiac nexus glia at the outflow tract are critical regulators of both the sympathetic and parasympathetic system. These data establish the crucial role of glia on cardiac homeostasis and provide a description of nexus glia in the PNS.”

“This is another example of how studying basic neurobiology can lead to the understanding of many different disorders,” Smith said. “I’m excited about the future.”

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