NANOG is a transcription regulator involved with inner cell mass and embryonic stem (ES) cell proliferation and self-renewal. It imposes pluripotency on ES cells and prevents their differentiation towards extra-embryonic endoderm and trophectoderm lineages. This protein blocks bone morphogenetic protein-induced mesoderm differentiation of ES cells by physically interacting with SMAD1 and interfering with the recruitment of coactivators to the active SMAD transcriptional complexes.