The CD90 marker, also known as Thy-1, is a widely studied protein found on the surface of many cells, playing a significant role in normal biological function and disease. It is classified as a cell surface glycoprotein, meaning it is a protein covered in sugar molecules that resides on the outer membrane of a cell. As a marker, CD90 provides researchers and clinicians with a molecular signpost to identify, isolate, and characterize various cell populations. Understanding this protein is fundamental to advancing fields like regenerative medicine, immunology, and cancer research.
Defining CD90 and Its Structure
The official nomenclature is Cluster of Differentiation 90 (CD90), historically known as Thy-1 due to its initial discovery on mouse thymocytes, a type of T cell. The gene responsible for its production is THY1, which is conserved across many vertebrate species. Structurally, CD90 is a small protein, typically weighing between 25 and 37 kilodaltons, with a significant portion of that mass contributed by its sugar modifications.
CD90 is unique because it is a glycophosphatidylinositol (GPI)-anchored protein, attached to the outer layer of the cell membrane by a lipid anchor rather than being embedded across it. This structure allows the protein to reside within specialized, dynamic regions called lipid rafts, which are rich in signaling molecules. CD90 is also characterized by a single immunoglobulin-like domain, placing it in the immunoglobulin superfamily of proteins.
CD90 expression is found on specific cell types, including T cells, hematopoietic stem cells, neurons, and endothelial cells. Important cell populations that express CD90 include fibroblasts, which build connective tissue, and mesenchymal stem cells. Its presence or absence is a defining feature used to distinguish these different cell populations in a laboratory setting.
Primary Biological Roles
CD90’s function centers on managing cell-to-cell and cell-to-matrix interactions. It acts as a ligand or a receptor, capable of binding to other molecules on neighboring cells or within the extracellular matrix. These interactions are crucial for processes such as cell adhesion, where cells stick to one another or to the surrounding tissue.
It is involved in signal transduction, relaying information from outside the cell to the inside, despite lacking an internal signaling tail. By clustering with other membrane components in lipid rafts, CD90 can modulate the activity of non-receptor tyrosine kinases, such as those in the Src family. This mechanism allows CD90 to influence various cellular behaviors, including cell migration and proliferation.
In the immune system, CD90 modulates the activation and proliferation of T cells. Within the nervous system, CD90 is highly expressed on mature neurons, particularly along the axon, where it influences nervous system development and synaptic plasticity. Its binding to integrins allows it to regulate the contraction and retraction of neuronal processes, contributing to nerve regeneration and axon growth.
Significance in Stem Cell Identification
The presence of CD90 is a defining characteristic for identifying and isolating Mesenchymal Stem Cells (MSCs). MSCs are multipotent progenitor cells capable of differentiating into various cell types, including bone, cartilage, and fat cells. For a cell to be classified as an MSC, organizations like the International Society for Cellular Therapy (ISCT) require it to be positive for CD90, CD73, and CD105, while being negative for certain blood cell markers.
Researchers use this marker to isolate and characterize MSCs from various tissues, such as bone marrow or adipose tissue, often using techniques like fluorescence-activated cell sorting (FACS). The expression level of CD90 can distinguish subpopulations within the MSC pool with different functional potentials. For example, high expression of CD90 (CD90-Hi cells) is associated with enhanced osteogenic differentiation, meaning they are more capable of forming bone.
The ability to isolate effective MSC populations holds implications for regenerative medicine. By selecting CD90-positive cells, scientists obtain a more homogeneous and effective cell source for therapies aimed at repairing damaged tissues, such as bone defects or heart muscle injury. The marker serves as a quality control measure, ensuring the cell product possesses the required regenerative abilities.
CD90 in Disease Pathology
The dysregulation of CD90 expression is implicated in the progression of several diseases, notably cancer and fibrosis. In cancer, CD90’s role can be complex, sometimes acting as both a promoter and a suppressor of tumor growth. High CD90 expression is frequently observed in aggressive cancers, such as hepatocellular carcinoma and some forms of lung cancer.
In these malignancies, CD90 is often associated with cancer stem cells, a small population of tumor cells that drive tumor initiation, resistance to therapy, and metastasis. Its expression in the tumor microenvironment, particularly on cancer-associated fibroblasts, is linked to increased tumor invasiveness and a poor patient prognosis. The protein facilitates cancer cell migration by mediating cell-matrix interactions, allowing them to spread.
CD90 also plays a role in the development of fibrosis, which is the excessive formation of connective tissue leading to scarring and organ stiffness. Fibrosis underlies diseases like pulmonary fibrosis and liver cirrhosis. In these conditions, CD90 acts as a marker for activated fibroblasts and myofibroblasts, the cells responsible for depositing scar tissue. The presence of CD90 on these cells contributes to their proliferation and migration, driving the pathological accumulation of extracellular matrix that ultimately impairs organ function.