Thy1 (CD90): Functions, Cellular Marker, and Disease Role

Thy1, or Cluster of Differentiation 90 (CD90), is a small glycoprotein anchored to the outer membrane of various cells. Composed of a protein and a carbohydrate chain, this molecule is found across many species, indicating its functions have been preserved throughout evolution. First discovered while studying immune cells in mice, Thy1 is expressed on cells like neurons, certain immune cells, and specific types of stem cells, playing different roles depending on its location.

Key Functions of Thy1

In the nervous system, Thy1 participates in the development and maintenance of neural circuits. It is found in high concentrations on neurons, where the protein influences the growth of axons—the long projections of nerve cells that transmit information. Thy1 helps ensure this wiring grows correctly during development and assists in its repair after injury. It accomplishes this by interacting with other molecules on neighboring cells and in the extracellular matrix. These interactions can either encourage or inhibit axonal growth, a regulatory role that helps the nervous system form and maintain its complex communication network.

Within the immune system, Thy1 is found on the surface of T-lymphocytes, or T-cells. Its presence was one of the first ways scientists learned to identify these cells, which is how the protein got its name—Thymocyte differentiation antigen 1. Thy1 is involved in the activation of T-cells, a process that initiates an immune response. When a T-cell encounters a foreign substance, Thy1 participates in signaling events that regulate the cell’s response, influencing its proliferation and engagement with other immune cells.

Thy1 as a Cellular Marker

In laboratory settings, one of the most widespread uses of Thy1 is as a cellular marker. A cell surface marker is a protein on the exterior of a specific cell type that acts like a name tag, allowing scientists to identify and sort it from a mixed population. This application is important in stem cell research. Mesenchymal stem cells (MSCs), which can differentiate into cell types including bone, cartilage, and fat cells, express high levels of Thy1. Researchers use this characteristic to isolate MSCs from tissues like bone marrow and confirm the identity and purity of the isolated stem cell population.

The primary technique for this cell sorting is called flow cytometry. In this process, cells are tagged with antibodies that specifically bind to Thy1 and are linked to a fluorescent dye. When a Thy1-positive cell passes through a laser, the dye lights up, and a machine detects this signal to count and physically separate the glowing cells from the non-glowing ones.

The Role of Thy1 in Disease Processes

The function of Thy1 can change in the presence of disease, where it often plays a complex and contradictory role. In cancer, Thy1’s involvement is not straightforward, as it can act as either a suppressor or a promoter of tumor growth depending on the specific type. For instance, in ovarian cancer, Thy1 is considered a tumor suppressor, and its absence is linked to a poorer prognosis. Conversely, in other cancers like melanoma, high expression of Thy1 is associated with increased invasion and metastasis. This is because its signaling may inhibit pathways for uncontrolled cell growth in some cellular environments, while in others, its interactions promote cell migration.

Thy1 is also implicated in the development of fibrosis, a condition characterized by the excessive formation of scar tissue in an organ. This process can affect organs like the lungs, liver, kidneys, and skin, leading to organ dysfunction. In many fibrotic diseases, Thy1 expression is elevated on fibroblasts, the cells responsible for producing collagen and other scar tissue materials. Studies show that Thy1 expression on fibroblasts promotes their activation into myofibroblasts, which are the primary drivers of tissue stiffening. For example, in the skin disease scleroderma, Thy1 expression is increased in the affected tissue and correlates with the severity of the fibrosis.

Therapeutic and Diagnostic Potential

Given its involvement in various diseases, Thy1 is being investigated for its potential in diagnostics and as a target for new therapies. The level of Thy1 expression on cells or in bodily fluids could serve as a diagnostic biomarker. For example, elevated Thy1 levels in skin biopsies correlate with fibrosis severity in patients with scleroderma. Researchers are also exploring how measuring Thy1 might help in diagnosing or staging certain cancers, as its expression is altered in many tumor types.

Beyond diagnostics, Thy1 presents a target for therapeutic intervention. For diseases where Thy1 promotes pathology, such as in specific cancers or fibrotic conditions, developing drugs that block its activity is a primary goal. A therapy that inhibits Thy1’s role in melanoma cell adhesion, for instance, could potentially reduce metastasis.

Conversely, in situations where Thy1 is beneficial, like its tumor-suppressing role in ovarian cancer or its function in nerve regeneration, therapies might be designed to enhance its presence or activity. The challenge lies in designing therapies that are highly specific to the targeted cell type and disease process.