According to a new study, nexus glial cells in the heart help control heart rate and drive cardiac cell maturation in the embryo. (Photo: A cross-section of the heart tissue showing nexus glia of the heart (green) interacting with neurons (blue) and other cardiac cells (red). Credit: Notre Dame/Nina Kikel-Coury)
A University of Notre Dame research team has found a new type of cardiac cell that may assist in controlling the heart’s rhythm and may hold the key to understanding some forms of congenital heart abnormalities and other heart disorders.
According to research conducted in the lab of Cody Smith, the Elizabeth and Michael Gallagher Associate Professor in the Department of Biological Sciences, the cells, dubbed nexus glia, mimic important glial cells called astrocytes in the brain. The heart rate rose when the newly found cells were eliminated, and the heart beat irregularly when they were deprived of a critical gene that promotes their proliferation.
Dr. Smith stated, “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. 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.”
While there is no direct link between the finding and congenital heart problems, these cardiac nexus glia cells are present in the heart’s outflow system, which is where many congenital heart disorders are found. The outflow tract is a developmental feature that contributes to a pathway linking the ventricles to the arteries leaving the heart. The cells were originally found in the hearts of zebrafish, and then verified in the hearts of mice and humans.
Astrocytes were formerly assumed to only be found in the brain and spinal cord of the central nervous system. The Smith lab had been puzzled as to why organs supplied with nerves by the peripheral nervous system, which includes all of the body’s remaining nerves, lacked astrocyte-like glial cells.
They play a crucial role in the formation and maintenance of neuronal circuits in the brain.
Why wouldn’t they exist in other places as well?
Nina Kikel-Coury, the paper’s lead author explained why she decided looking for these clubs in the first place, saying, “I thought that if we could find a new cellular piece to the cardiovascular puzzle, it could be foundational for future work.”
Kikel-Coury was specifically interested as to how these cells played a role in dysautonomia, a collection of medical diseases caused by malfunctions in the autonomic nerve system. Postural orthostatic tachycardia syndrome (POTS) is one of the disorders under this umbrella, of which Kikel-Coury suffers from herself. POTS causes lightheadedness, fainting, and a sudden rise in heart rate.
While it’s possible that POTS is connected to the novel cell revealed in the study’s fundamental research, Smith suggests that it’s too early to know.
“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.”
“This is another example of how studying basic neurobiology can lead to the understanding of many different disorders,” Smith said.
The study was published in PLOS Biology, on November 18th, 2021.
Abstract. Glial cells are essential for functionality of the nervous system. 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. Nexus glia are labeled with gfap, glast, and glutamine synthetase, markers that typically denote astroglia cells. 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.
Kikel-Coury NL, Brandt JP, Correia IA, O’Dea MR, DeSantis DF, et al. (2021) Identification of astroglia-like cardiac nexus glia that are critical regulators of cardiac development and function. PLOS Biology 19(11): e3001444. https://doi.org/10.1371/journal.pbio.3001444
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