April 23, 2024

Little-Known Glial Cells Are Critical Regulators of Heart Development and Function

A section of heart tissue that reveals the nexus glia of the heart (green) interact with neurons (blue) and heart cells (red), likely to regulate heart function. Credit: Nina Kikel-Coury, CC BY 4.0
Discovery recommends glial cells might be crucial in other organs.
Glial cells in the heart aid manage heart rate and rhythm, and drive its advancement in the embryo, according to a new research study publishing today (November 18th, 2021) in the open-access journal PLOS Biology by Nina Kikel-Coury, Cody Smith and colleagues at the University of Notre Dame. The discovery offers the most comprehensive portrait yet of a vital population of cells that had been previously improperly comprehended.
Glia are a varied set of cell types, initially called after the Greek word for glue, and include cells that surround and nurture nerve cells, and others that install immune responses within the main nerve system. In the peripheral anxious system, glia are probably active and present in numerous organs, including the gut, pancreas, spleen, and lungs, although their function is not clear.

Recently, a cell population in the heart that reveals a known astroglial marker has actually been reported, and a part of the establishing heart called the outflow tract consists of a group of cells derived from an embryonic structure called the neural crest, which is the source of a lot of peripheral glial cells.
These intriguing clues led the authors to look more deeply at the identity and function of these cells. Beginning in zebrafish, they discovered a plentiful group of cells in the hearts ventricles that produced glial fibrillary acid protein (GFAP), a traditional marker of glia. GFAP-positive cells were likewise found in the hearts of mice and people. Those cells were focused in the so-called outflow system in early advancement, a structure that forms in the heart during advancement and adds to the pathway that links the ventricles to the arteries leaving the heart. Eliminating these cells increased the rate of nerve development in the embryonic heart, suggesting they play a repressive or delaying role in heart innervation. By a range of techniques, including tracking separately labeled cells as they moved, the researchers showed that the glial cells that settle in the outflow tract start their journey in the neural crest. They called these cells nexus glia.
What is the function of these glial cells in the fully grown heart? When the authors removed the cells, the heart rate increased; when the cells were reduced by depriving them of a key gene that drives their glial advancement, the resulting heart beat irregularly.
The outcomes considerably expand the understanding of the function of glial cells in the heart and suggest that glia may likewise play vital functions in the advancement and function of other organs where they have been glimpsed. “Our findings show an under-explored and comprehensive network of organ-associated glia that have practical roles dependent upon the environment,” Smith stated. “Further understanding of these specialized astroglial populations is for that reason essential, offered their potential effect on organ physiology.”
Smith includes, “Astrocyte-like cells in the PNS are poorly comprehended. We show that an astrocyte-like cell functions early in development to control autonomic-nervous system control of the heart.”
Reference: “Identification of astroglia-like heart nexus glia that are important regulators of cardiac advancement and function” by Kikel-Coury NL, Brandt JP, Correia IA, ODea MR, DeSantis DF, Sterling F, et al., 18 November 2021, PLOS Biology.DOI: 10.1371/ journal.pbio.3001444.
Financing: This work was supported by the University of Notre Dame, the Elizabeth and Michael Gallagher Family (CJS), Centers for Zebrafish Research and Stem Cells Regenerative Medicine at the University of Notre Dame (CJS), the Alfred P. Sloan Foundation (FG-2017-9531)( CJS) and the National Institute of Health (DP2NS117177)( CJS). The funders had no function in study design, information collection and analysis, decision to release, or preparation of the manuscript.

Beginning in zebrafish, they found an abundant group of cells in the hearts ventricles that produced glial fibrillary acid protein (GFAP), a classic marker of glia. Those cells were focused in the so-called outflow tract in early development, a structure that forms in the heart during advancement and contributes to the path that connects the ventricles to the arteries leaving the heart. Eliminating these cells increased the rate of nerve development in the embryonic heart, recommending they play a repressive or postponing function in cardiac innervation. When the authors got rid of the cells, the heart rate increased; when the cells were minimized by denying them of a crucial gene that drives their glial development, the resulting heart beat irregularly. The outcomes significantly broaden the understanding of the role of glial cells in the heart and recommend that glia might also play important roles in the advancement and function of other organs where they have actually been glimpsed.