For the first time, Francis Crick Institute researchers have discovered stem cells in the human thymus. These cells provide a possible new target for research into immunological disorders, cancer, and immune system stimulation.
Thymocytes (the gland’s cells) grow into T cells, specialized immune cells essential to battling diseases, in the thymus, a gland found in the front of the chest. The thymus has a distinct and intricate three-dimensional structure, which includes an epithelium (a layer of cells that can direct T-cell development) that wraps around the thymocytes and creates a mesh throughout the entire organ.
Since it is relatively inaccessible and diminishes with age, and because its role was identified just a few decades ago, the thymus has received less attention than other organs. Until now, experts assumed it only included progenitors developing during fetal development rather than ‘real’ epithelial stem cells.
However, these discoveries, published on August 30th, 2023, in Developmental Cell, indicate the presence of self-renewing stem cells for the first time, which give birth to thymic epithelial cells that instruct thymocytes to become T-cells. This shows that the thymus has an essential, regenerative role that can be used to strengthen the immune system after childhood.
The researchers evaluated these stem cells based on the expression of particular proteins in the human thymus throughout their investigations. They discovered stem-cell niches (areas where stem cells congregate) in the thymus in two places: underneath the organ capsule, or outer layer, and surrounding blood vessels in the medulla, or central part.
They revealed that thymic stem cells contribute to the environment by creating extracellular matrix proteins, which serve as their support system.
It was discovered that these stem cells, called Polykeratin cells, express a multitude of genes that enable them to give birth to various cell types not previously thought to have a common origin by employing cutting-edge tools to analyze gene expression in single cells and tissue sections. They can differentiate into epithelial, muscular, and neuroendocrine cells, emphasizing the role of the thymus in hormone control.
The scientists were able to demonstrate that thymus stem cells can be significantly enlarged by isolating Polykeratin stem cells in a dish. They showed that a single stem cell could create all the complicated cells in the thymus epithelium, showing a tremendous and unrealized regeneration potential.
It is paradoxical that stem cells in the thymus–—an organ which reduces in size as we get older—regenerate just as much as those in the skin—an organ which replaces itself every three weeks. The fact that the stem cells give rise to so many different cell types hints at more fundamental functions of the thymus into adulthood.
Roberta Ragazzini, Study First Author and Postdoctoral Research Associate, The Francis Crick University
It is known that the thymus’ activity is closely controlled in adults, giving the immune system just enough boost to combat infections without going beyond and targeting the body’s own cells.
However, in some people, the thymus fails to function correctly or their immune system is not as strong as it should be. According to the findings, it would be advantageous in certain situations to encourage the stem cells to reconstruct the thymus and strengthen their immune system.
This research is a pivotal shift in our understanding of why we have a thymus capable of regeneration. There are so many important implications of stimulating the thymus to produce more T cells, like helping the immune system respond to vaccinations in the elderly or improving the immune response to cancer.
Paola Bonfanti, Senior Group Leader, Epithelial Stem Cell Biology and Regenerative Medicine Laboratory
The next step for the researchers is to examine the characteristics of thymic stem cells throughout life and how to alter them for possible therapeutics.
Ragazzini, R., et al. (2023). Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus. Developmental Cell. doi.org/10.1016/j.devcel.2023.08.017