The Nanog gene profoundly influences cell identity. It acts as a major factor in determining whether a cell maintains its unspecialized state or begins the process of becoming a specific tissue type. Discovered for its unique ability to promote pluripotency, Nanog plays a central role in controlling cell development and regeneration. Its presence or absence can alter the fate of a cell, making it a focus of scientific study.
Nanog’s Core Role in Stem Cells
Nanog’s most recognized function is sustaining the pluripotency and self-renewal capabilities of embryonic stem cells (ESCs). Pluripotency refers to a stem cell’s capacity to differentiate into any cell type. Nanog actively works to prevent these cells from specializing, thus maintaining their undifferentiated state.
Nanog functions within a complex regulatory network alongside other transcription factors like Oct4 and Sox2. These three factors, Oct4, Sox2, and Nanog, form a core transcriptional circuit that promotes their continuous self-renewal. Oct4 and Sox2 bind to the Nanog promoter to stimulate its transcription, indicating a coordinated effort to maintain pluripotency.
Nanog also represses genes that initiate differentiation, such as GATA6, which represses GATA4, inhibiting ESC differentiation. The levels of these interacting factors are important for stem cell maintenance. While Oct4 and Sox2 levels are stable in undifferentiated ESCs, Nanog levels can vary, with higher levels correlating with more efficient self-renewal. This ensures that ESCs retain their ability to proliferate indefinitely.
Nanog Beyond Stem Cells
Beyond embryonic stem cells, Nanog’s function extends to other biological contexts, including germline development and certain cancer types. In germline development, Nanog protein is detected in germline stem cells within the developing testis. This suggests a role in forming cells that give rise to sperm or eggs.
Nanog also re-emerges in certain cancer cells, where its expression contributes to hallmarks of malignancy. High Nanog expression in cancer is linked to advanced disease stages, poor differentiation, reduced patient survival, and increased therapy resistance. Nanog enables cancer cells to acquire stem-like properties, fueling tumor growth, promoting metastasis, and recurrence after treatment.
For instance, Nanog has been shown to promote chemoresistance and increased cell migration in various cancers, including lung adenocarcinoma, breast cancer, and ovarian cancer. In ovarian cancer, elevated Nanog levels are associated with high-grade cancer, severe histological subtypes, and reduced sensitivity to chemotherapy. The gene’s ability to confer aggressive traits makes it a subject of intense investigation in cancer research.
Understanding Nanog’s Medical Significance
Understanding Nanog’s functions has implications for human health and medicine, particularly in regenerative medicine, drug discovery, and cancer therapy. In regenerative medicine, Nanog is a gene that is used to create induced pluripotent stem cells (iPSCs). These iPSCs are generated by reprogramming adult somatic cells, and Nanog’s involvement in this process is important for establishing their pluripotent state. This reprogramming capability opens avenues for generating patient-specific cells and tissues for transplantation and disease modeling, potentially bypassing ethical concerns associated with embryonic stem cells.
Nanog’s role in maintaining stemness and promoting aggressive characteristics in cancer cells positions it as a target for new therapies. Given its association with tumor growth, therapy resistance, and metastasis, researchers are exploring ways to modulate Nanog activity to combat cancer.
For example, studies have shown that inhibiting Nanog expression can suppress tumor growth and metastasis in preclinical models of colorectal cancer.
The gene’s re-expression in precancerous lesions, but not in most normal adult tissues, makes it a promising biomarker for early cancer detection and differentiation between true dysplasia and reactive conditions. Furthermore, understanding how Nanog influences metabolic pathways in cancer cells, such as oxidative phosphorylation and fatty acid oxidation, could lead to the development of drugs that disrupt these processes and make cancer cells more susceptible to treatment. This makes Nanog a complex but interesting target for future medical interventions.