NANOG

NANOG is a homeobox-containing transcription factor encoded by the NANOG gene in mammals. It is a key component of the core pluripotency network that maintains the self-renewal and undifferentiated state of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). In many species, NANOG works alongside Oct4 (POU5F1) and Sox2 to activate pluripotency-associated genes and repress differentiation programs. NANOG is expressed in the inner cell mass of the pre-implantation embryo and in ESCs, and its expression declines as cells differentiate toward primitive endoderm and other lineages. Loss of NANOG function in mouse ESCs leads to differentiation, whereas sustained NANOG expression helps sustain pluripotency and supports reprogramming of somatic cells.

The NANOG protein contains a homeobox DNA-binding domain and functions as a transcription factor, influencing a network of downstream targets that regulate chromatin state, metabolism, and the cell cycle to support pluripotency. The gene has multiple processed pseudogenes in the genome (NANOGP family), and several species-specific paralogs may exist; some pseudogenes and retrogenes can be expressed in cancers, contributing to varied expression patterns.

In research, NANOG is used as a marker of undifferentiated pluripotent cells and is studied in the context of development, stem cell biology, and cancer. Therapeutic applications focus on improving reprogramming efficiency and understanding differentiation pathways, though clinical use remains exploratory.