NANOG is a homeobox transcription factor that plays a crucial role in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). It is named after the mythical Celtic land of eternal youth, “Tír na nÓg,” reflecting its role in sustaining the undifferentiated state of stem cells. The human NANOG gene is located on chromosome 12p13.31 and consists of four exons and three introns .
The NANOG protein is composed of 305 amino acids and includes a central homeodomain (HD) that is essential for its function. This homeodomain consists of an unstructured N-terminal arm and a bundle of three α-helices (H1–H3) interlinked by loops . NANOG expression is predominantly observed in embryonic stem cells and certain pluripotent cancer cells, while it is suppressed in most adult tissues .
NANOG is vital for the early stages of embryogenesis. During mouse embryonic development, the absence of NANOG expression in the inner cell mass results in the failure to produce the epiblast, leading to the formation of parietal endoderm-like cells instead . In human ESCs, NANOG is a key player in the transcriptional pluripotency regulatory network, working alongside other factors such as OCT4 and SOX2 .
Recombinant human NANOG is typically expressed in Escherichia coli (E. coli) and purified to high levels of homogeneity. The recombinant protein retains its secondary structure and biological activity, making it suitable for various research applications . The recombinant form of NANOG is often used to study its role in cellular processes, including stemness, tumor progression, and migration .
NANOG’s ability to maintain pluripotency and self-renewal makes it a valuable tool in regenerative medicine and cell therapy. It is also involved in the nuclear reprogramming necessary for forming induced pluripotent stem cells (iPSCs), which have enormous potential for therapeutic applications . Additionally, NANOG is linked to cellular multipotency and plays crucial roles in cancer progression, highlighting its potential as a therapeutic target for various malignancies .