1O4X, 2LE4665720674ENSG00000181449ENSMUSG00000074637P48431P48432NM_003106NM_011443NP_003097NP_035573SRY (sex determining region Y)-box 2, also known as SOX2, is a transcription factor that is essential for maintaining self-renewal, or pluripotency, of undifferentiated embryonic stem cells.

[5] Sox2 is a member of the Sox family of transcription factors, which have been shown to play key roles in many stages of mammalian development.

[11] The discovery that expression of only four transcription factors was necessary to induce pluripotency allowed future regenerative medicine research to be conducted considering minor manipulations.

Loss of pluripotency is regulated by hypermethylation of some Sox2 and Oct4 binding sites in male germ cells[12] and post-transcriptional suppression of Sox2 by miR134.

[8] The loss of Sox2 has also been shown to affect naïve pluripotency, with Sox2-depleted mouse embryonic cells becoming able to differentiate into extraembryonic trophoblast.

[15] Deficiency of Sox2 in mice has been shown to result in neural malformities and eventually fetal death, further underlining Sox2's vital role in embryonic development.

[16] In neurogenesis, Sox2 is expressed throughout developing cells in the neural tube as well as in proliferating central nervous system progenitors.

The difference in brain size between humans and apes, for instance, has been linked to mutations in the gene Asb11, which is an upstream activator of SOX2 in the developing neural system.

[23] Under normal conditions, Sox2 is critical for maintaining self-renewal and appropriate proportion of basal cells in adult tracheal epithelium.

[25] Sox2 is a key upregulated factor in lung squamous cell carcinoma, directing many genes involved in tumor progression.

It has therefore been suggested that transcriptional repression of Sox2, mediated by the thyroid hormone signaling axis, allows for neural stem cell commitment and migration from the sub-ventricular zone.