Eliminated cells initiate a protective mechanism

Sayak Banerjee, Amity University Kolkata

Human Epithelial Tissue Integrity

Human epithelia are tissues that are seen in various parts of the body in the form of internal mucosa, epidermis, etc. They are made up of several layers of neighbouring cells and they act not only as a physical barrier but also as a chemical barrier. This function as a barrier is continually put to test by both the outer environment and their renewal. Tissue renewal incorporates the formation of new cells by the simultaneous process of cell division along with the elimination of dead cells. This is done without putting the tissue integrity, form, and connectivity. The mechanism that controls the potential of epithelia in the regulation of their integrity involving a large number of cells remains unknown. Although this process takes place constantly during embryogenesis or adult tissue maintenance, the mechanism of integrity is poorly understood. 

The Protective Mechanism of cells

Researchers from the Institut Pasteur and the CNRS today have come up with a new process that enables the eliminated cells to temporarily protect their neighbours from cell death, thus retaining tissue integrity. This mechanism of protection is important and if it is interrupted it can result in a short-term loss of connectivity. It was observed that in case of deactivation of the process, there would be simultaneous death of several neighbouring cells thereby compromising tissue integrity. This lack of integrity could give rise to chronic inflammation in the tissue. They used Drosophila to determine the mechanisms involved in epithelial tissue integrity and connectivity as it inherits an epithelial architecture that is similar to that of humans.

Employing protein-sensitive fluorescent markers, the scientists discovered that when a cell dies, a signalling pathway is activated in the neighbouring cells. This cell activation signalling pathway is known as the EGFR-ERK pathway and it is responsible for the regulation of cell survival. Therefore, it prevents the simultaneous elimination of a group of cells for around one hour. They also observed that hindering this protective mechanism brings a severe effect on the epithelial tissue. It is characterized by random cell elimination and simultaneous elimination of neighbouring cells giving rise to continuous loss of connectivity. The research team used a novel optogenetic tool that can control cell death in time and space and avoid the protective mechanism. Using the tool they found that epithelial tissue is highly susceptible to the spatial distribution of eliminated cells. Despite withstanding a huge amount of elimination of cells, the epithelial integrity is affected if only three neighbouring cells undergo simultaneous elimination.

Inference from their Findings

The findings confirmed that a certain mechanism is needed to be developed by the tissue to prevent the elimination of neighbouring cells. The observations exhibited the surprising self-organizing potential of epithelial tissues which allows them to resist stressful conditions. The researchers regarded this process to be conserved during evolution. With the reference of another study, they concluded that the protective mechanism is conserved between species separated by millions of years. Future research might disclose whether the interruption in this protective mechanism causing frequent loss of connectivity in the epithelial tissue could be the main reason behind chronic inflammation, a phenomenon resulting in multiple diseases that are presently the leading cause of deaths globally.

Also read: Liquid biopsy and droplet digital PCR help to detect Colorectal cancer

Source: Valon, L., Davidović, A., Levillayer, F., Villars, A., Chouly, M., Cerqueira-Campos, F., & Levayer, R. (2021). Robustness of epithelial sealing is an emerging property of local ERK feedback driven by cell elimination. Developmental Cell, 56(12), 1700-1711.e8. https://doi.org/10.1016/j.devcel.2021.05.006

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About the author: Sayak Banerjee is a 3^rd-year Biotechnology Student with a great interest in Immunology and Molecular genetics. He is a creative scientific writer in Bioxone with an inclination towards gaining knowledge regarding vast sections of Biotechnology and emphasizing himself in various wet lab skills.