Thy1, also called CD90, is a small protein anchored to the outer surface of cells across a remarkably wide range of tissues, from developing immune cells in the thymus to neurons in the brain, fibroblasts in the lungs, and stem cells in the bone marrow. First identified decades ago as a marker on mouse T cells (hence “thymocyte differentiation antigen 1”), CD90 has turned out to be far more than a passive label. It actively shapes how cells signal, migrate, stick together, and respond to injury, and its presence or absence on particular cell types now helps researchers and clinicians identify stem cell populations, predict fibrosis progression, and even track aggressive cancer subtypes.
What CD90 Actually Is
CD90 is a glycoprotein, meaning it is a protein decorated with sugar chains, that sits on the outside of the cell membrane. Instead of threading through the membrane like most surface proteins, CD90 is tethered by a lipid tail called a GPI anchor. That anchoring method matters: it parks CD90 in specific cholesterol-rich patches of the membrane known as lipid rafts, and from those patches it can organize signaling molecules and influence how the cell responds to its surroundings. In fibroblasts, for instance, the GPI anchor is required for CD90 to trigger the activation of enzymes involved in cell movement and the remodeling of attachment sites that connect a cell to its surroundings.1PubMed. Thy-1, via its GPI anchor, modulates Src family kinase and focal adhesion kinase phosphorylation and subcellular localization, and fibroblast migration, in response to thrombospondin-1/hep I
CD90 does not work alone. It forms complexes with integrins and another surface molecule called syndecan 4, creating a three-part signaling unit that can send messages both into and out of the cell.2PubMed Central. Thy-1 (CD90), Integrins and Syndecan 4 are Key Regulators of Skin Wound Healing This arrangement lets CD90 influence diverse processes, from wound repair to immune cell trafficking, depending on which partner molecules are nearby and what tissue the cell is sitting in.
CD90 as a Cellular Marker
One of CD90’s best-known practical uses is as a surface tag for identifying specific cell populations. In stem cell biology, CD90 is part of the standard panel researchers use to confirm that they are looking at mesenchymal stem cells. Human and mouse mesenchymal stem cells reliably express CD90 along with CD44, CD105, and CD166, while lacking the blood-cell markers CD34 and CD45.3PubMed Central. Characterization and Classification of Mesenchymal Stem Cells in Several Species Using Surface Markers for Cell Therapy Purposes This positive-negative combination is how labs worldwide verify that the cells they have isolated are genuine mesenchymal stem cells rather than blood-forming cells or other contaminants.
CD90 also marks a rare and important subset of blood-forming stem cells. The population defined as CD34-positive, CD38-negative, CD90-positive, and CD45RA-negative represents some of the most primitive hematopoietic stem cells, the cells capable of rebuilding the entire blood system after a bone marrow transplant. Researchers have found this population in cord blood, mobilized peripheral blood, and even in samples from patients with chronic myelogenous leukemia, and have confirmed that these cells can repopulate the bone marrow of recipient mice over the long term.4Blood Cancer Journal. Further phenotypic characterization of the primitive lineage− CD34+CD38−CD90+CD45RA− hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patients with chronic myelogenous leukemia
Beyond stem cells, CD90 shows up on neurons, activated endothelial cells lining blood vessels, certain subsets of fibroblasts, and some kidney cells. This broad distribution is part of why it keeps appearing in studies of very different diseases: wherever CD90-positive cells sit, the protein influences local behavior.
Immune Functions and T Cell Development
CD90 was originally discovered on T cells, and its role in the immune system remains one of the best-studied aspects of the protein. Experiments with mice that completely lack CD90 revealed something counterintuitive: rather than losing immune function, these animals showed overactive T cell signaling. Their developing T cells in the thymus displayed exaggerated responses when the T cell receptor was triggered, including stronger activation of the enzyme p56lck, increased calcium fluxes, and greater cell proliferation. But this hyperactivity came at a cost. Maturation from an early stage to a mature T cell was impaired, likely because too-strong signaling pushed developing cells into inappropriate death. Older mice lacking CD90 were also prone to T cell lymphomas.5PubMed. Thymocytes in Thy-1-/- mice show augmented TCR signaling and impaired differentiation In other words, CD90 acts as a brake on T cell activation, helping to set the threshold for how strong a signal needs to be before the cell responds. Without that brake, T cells become hyperreactive and prone to going wrong.
CD90 also plays a direct role in how immune cells get to sites of inflammation. On activated endothelial cells, CD90 serves as a docking partner for Mac-1, an integrin found on white blood cells like monocytes and neutrophils. This interaction helps leukocytes stick to vessel walls and then migrate through the endothelial layer into inflamed tissue.6PubMed. Human Thy-1 (CD90) on activated endothelial cells is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18) So CD90 shapes immunity in at least two distinct ways: it calibrates the sensitivity of developing T cells and it physically guides mature immune cells to the right location.
The Neurobiology Side
Neurons are among the richest sources of CD90 in the body, and the protein’s function there appears quite different from its immune roles. When a neural cell line expressing CD90 was grown on mature brain-supporting cells called astrocytes, CD90 actively blocked the extension of nerve fibers. The inhibition was specific to mature astrocytes; it did not occur on other cell types like Schwann cells or embryonic glia. Adding tiny amounts of soluble CD90 reversed the block.7PubMed. Selective inhibition of neurite outgrowth on mature astrocytes by Thy-1 glycoprotein The implication is that CD90 may help stabilize existing neural connections in the adult brain by preventing neurons from sprouting new branches into astrocyte-rich territory. The flip side, though, is that this same mechanism could contribute to why nerve fibers fail to regrow after injury in the adult central nervous system.
The abundance of CD90 on neurons has also made its gene promoter a workhorse tool in neuroscience research. When scientists want to express a foreign protein specifically in neurons, the Thy1 promoter is one of the go-to choices because it drives strong, neuron-selective expression. Comparison studies found that among several neuron-specific promoters, only the Thy1 promoter produced transgene levels comparable to or higher than the levels of the normal mouse protein.8Neurobiology of Aging. Expression of APP in transgenic mice: a Comparison of neuron-specific promoters This led to the creation of widely used mouse lines, including the Thy1-GCaMP6 mice that allow researchers to watch brain activity in real time by expressing calcium-sensitive fluorescent proteins in neurons.9PLOS ONE. Thy1-GCaMP6 Transgenic Mice for Neuronal Population Imaging In Vivo These tools have been central to modern systems neuroscience, used to study everything from sensory processing to decision-making.
Pulmonary Fibrosis and the Loss of CD90
Perhaps nowhere is CD90’s role in disease more compelling than in pulmonary fibrosis, a condition in which lung tissue becomes progressively scarred and stiff. In healthy lungs, most fibroblasts express CD90. In fibrotic lungs, fibroblasts within the active scarring regions, called fibroblastic foci, have lost CD90 expression. This loss is not random damage; it happens through an epigenetic mechanism. The promoter region of the Thy1 gene becomes hypermethylated, which silences the gene without altering the DNA sequence itself. Critically, treating these silenced fibroblasts with drugs that block DNA methylation can restore CD90 expression.10American Journal of Respiratory Cell and Molecular Biology. Thy-1 Promoter Hypermethylation: A Novel Epigenetic Pathogenic Mechanism in Pulmonary Fibrosis
What drives this silencing? The signaling molecule TGF-β1 appears to be a key culprit. In aging mice, researchers found an increase in fibroblasts lacking CD90 alongside rising TGF-β1 levels. When they treated lung fibroblasts with TGF-β1 in the lab, CD90 expression dropped, and this was accompanied by activation of the enzymes that add methyl groups to DNA. Co-treating with a methylation inhibitor prevented the loss of CD90.11PubMed Central. TGF-β1 epigenetically modifies Thy-1 expression in primary lung fibroblasts This creates a vicious cycle: TGF-β1 silences CD90, and losing CD90 makes fibroblasts more susceptible to further TGF-β1 signaling.
The reason that cycle matters mechanically is that CD90 normally holds fibroblasts in check. CD90 interacts with the integrin αvβ5 on the fibroblast surface, and that interaction prevents the fibroblast from mechanically activating latent TGF-β1 stored in the surrounding tissue. When CD90 is lost, αvβ5 is free to pull on and activate latent TGF-β1, which then drives the fibroblast to differentiate into a myofibroblast, the contractile, collagen-producing cell type that actually builds scar tissue.12Journal of Biological Chemistry. Thy-1-Integrin αvβ5 Interactions Inhibit Lung Fibroblast Contraction-induced Latent Transforming Growth Factor-β1 Activation and Myofibroblast Differentiation The fact that this silencing is epigenetic, and therefore potentially reversible, has made CD90 a subject of real therapeutic interest in fibrotic disease.
Cancer Stem Cells and CD90
CD90 occupies an unusual and sometimes contradictory position in cancer biology. In some tumor types it marks the most dangerous cells; in others, it appears to suppress tumor growth.13PubMed. Multiple roles of CD90 in cancer The best-established oncogenic role is in liver cancer. In hepatocellular carcinoma cell lines, CD90-positive cells can form tumors when transplanted into immunodeficient mice, while CD90-negative cells cannot. Among liver cancer patients, all tumor specimens and over 90% of blood samples contained a CD90-positive, CD45-negative population capable of generating tumor nodules in mice, and this capacity persisted through serial transplantation, a hallmark of cancer stem cells.14PubMed. Significance of CD90+ cancer stem cells in human liver cancer CD90-positive liver cancer cells are associated with higher metastatic potential and upregulation of genes related to inflammation, drug resistance, and cell proliferation. CD90 expression is also enriched in poorly differentiated tumors and tracks with a worse prognosis.15PubMed Central. Clinical Significance of CD90(+) Circulating Tumor Cells as Dynamic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab/Bevacizumab and Lenvatinib
These findings have led to early efforts to target CD90-positive cancer stem cells directly. One approach used antibody-coated, heat-releasing magnetic nanoparticles (thermosensitive magnetoliposomes) that home in on CD90. In both cell culture and animal models, these targeted particles showed greater inhibition of liver cancer stem-like cells than untargeted versions.16PubMed Central. Effective elimination of liver cancer stem-like cells by CD90 antibody targeted thermosensitive magnetoliposomes Separately, blocking CD90 with short hairpin RNA or antibodies reduced the expression of another stemness marker, CD133, and suppressed the ability of liver cancer cells to grow without a solid surface to attach to, a property linked to tumor-forming ability.17PubMed Central. Therapeutics targeting CD90-integrin-AMPK-CD133 signal axis in liver cancer
CD90 in the Tumor Microenvironment
CD90 does not just mark cancer cells themselves. It also identifies a subset of cancer-associated fibroblasts (CAFs), the support cells that tumors recruit to sustain their growth. In lung adenocarcinoma, CD90-positive CAFs were found within stromal bands and at the invasive edges of tumors, and a gene expression signature associated with these cells correlated with shorter overall survival across multiple patient cohorts.18Scientific Reports. Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis
In gastric cancer, a similar pattern emerges. When researchers knocked down CD90 in CAFs, the fibroblasts became less activated. Fluid collected from those CD90-deficient CAFs lost much of its ability to drive cancer cell proliferation and invasion, inhibited new blood vessel formation, and allowed immune killer T cells to more effectively destroy tumor cells while boosting their secretion of the immune-activating molecule IFN-γ.19PubMed Central. Integrated Transcriptomic Analysis and Machine Learning Identify THY1 as a Key Regulator of Cancer-Associated Fibroblast Infiltration, Promoting Malignant Progression and Immune Escape in Gastric Cancer CD90-positive gastric CAFs have also been linked to drug resistance: they appear to deliver cargo via tiny membrane-bound particles called extracellular vesicles that make tumor cells resistant to the chemotherapy drug oxaliplatin.20PubMed. COL11A1-packaged extracellular vesicles from THY1(+) cancer-associated fibroblasts confer oxaliplatin resistance and unfavorable prognosis in gastric cancer
The extracellular vesicle connection extends to breast cancer as well. In triple-negative breast cancer cells, knocking down CD90 disrupted the internal scaffolding of the cell, downregulated key growth-promoting signals, and dramatically altered the vesicles the cells released. The vesicles became larger and more irregular, lost important surface markers, and lost their ability to stimulate blood vessel growth or fibroblast migration. Instead, they triggered disorganization and death of endothelial cells in laboratory models.21Cancer Research. CD90 knockdown alters extracellular vesicles-mediated communication driving angiogenesis and tumor-stroma crosstalk in triple-negative breast cancer This suggests CD90 helps tumors communicate with their surrounding tissue, and disrupting that communication could undermine the tumor’s support network.
Soluble CD90 as a Diagnostic Biomarker
CD90 is not only found on cell surfaces. A soluble form (sCD90) circulates in the blood and appears in urine, and its levels shift in certain diseases, raising interest in its use as a diagnostic tool. In endometriosis, a condition that is notoriously difficult to diagnose without surgery, serum sCD90 levels were roughly three and a half times higher in patients than in healthy controls. Using a cutoff value, the test achieved about 70% sensitivity and 93% specificity, meaning it correctly identified most patients while rarely flagging healthy individuals by mistake.22PubMed Central. Evaluation of Soluble CD90: Potential for Diagnostic Significance in Endometriosis Patients
In systemic sclerosis, a connective-tissue disease that can affect the lungs, serum sCD90 levels were elevated compared to healthy volunteers, and patients who had developed pulmonary fibrosis or pulmonary arterial hypertension had even higher levels than those without lung involvement.23PubMed. Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis This pattern parallels the role of CD90 loss in pulmonary fibrosis described earlier: as fibroblasts shed CD90 or release it through tissue remodeling, circulating levels may reflect the degree of fibrotic activity in the lungs.
Urinary sCD90 has shown promise in diabetic kidney disease. Patients with kidney damage had higher urinary sCD90 levels than those with diabetes alone or healthy individuals, and elevated levels independently predicted worse kidney outcomes over time, even after adjusting for other risk factors.24PubMed Central. Urinary soluble CD90 predicts renal prognosis in patients with diabetic kidney disease None of these biomarker findings are ready for routine clinical use yet, but they point to sCD90 as a versatile indicator of tissue remodeling and fibrotic processes across organs.
An Unexpected Role in Viral Entry
CD90 has also turned up in infectious disease research. Human cytomegalovirus, a common virus that usually stays dormant but can cause serious illness in immunocompromised individuals, uses CD90 to get into cells. Through a series of experiments blocking, removing, and restoring CD90, researchers showed that the protein helps the virus enter cells at the initial attachment and entry stage, and that this role is especially important when the virus is present at low concentrations, as it typically is during natural infection.25PubMed Central. THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection This finding adds CD90 to the list of host surface molecules that viruses have co-opted for entry, alongside better-known receptors used by HIV and influenza.
Evolutionary Conservation
One of the more striking things about CD90 is how old it is. Using antibodies raised against rat CD90, researchers detected cross-reactive proteins of similar size (22 to 25 kilodaltons) in mammals, birds, reptiles, fish, and even invertebrates including earthworms, snails, oysters, and a locust species. The authors concluded that among immune-related genes sharing structural features with antibodies, CD90 is the most conserved across the animal kingdom.26PubMed. Evolutionary conservation of brain Thy-1 glycoprotein in vertebrates and invertebrates Molecular analysis of fish genomes shows that while the amino acid sequence has diverged substantially between fish and mammals, the gene’s overall structure and chromosomal neighborhood remain recognizable.27PubMed. Evolutionary analysis and expression of teleost Thy-1 The fact that CD90 has been retained from invertebrates through humans over hundreds of millions of years of evolution underscores that whatever it does, organisms that lose it are at a real disadvantage. That deep conservation likely reflects its involvement in fundamental processes like cell adhesion, signaling, and tissue organization rather than any single specialized immune or neural function.
CD90 on Extracellular Vesicles
Extracellular vesicles, the small membrane-bound packages that cells release to communicate with each other, carry surface markers from their parent cell. When mesenchymal stem cells shed vesicles, those particles carry CD90 along with CD44 and CD73, while lacking the blood cell markers CD34 and CD45, mirroring the surface profile of the cells they came from.28PubMed. Multi-parametric analysis of circulating extracellular vesicles by flow cytometry This has practical value: researchers can use CD90 to identify which vesicles in a blood sample came from mesenchymal stem cells versus other cell types, enabling more precise analysis of cell-to-cell communication in both health and disease. Combined with the findings in breast and gastric cancer showing that CD90 shapes the cargo and function of tumor-derived vesicles, the protein is emerging as a gatekeeper of vesicle-mediated signaling, not just a passive passenger.