Stem cell pluripotency LIF (Leukemia inhibitory factor) signaling, which maintains pluripotency in mouse embryonic stem cells, activates<unk>  downstream of the JAK-STAT signaling pathway and subsequent activation of Klf4 (a member of the family of Kruppel-like factors). Oct-4,<unk>  and Nanog positively regulate transcription of all pluripotency circuitry proteins in the LIF pathway. NPM1, a transcriptional regulator involved in cell proliferation, individually forms complexes with<unk> , Oct4 and Nanog in embryonic stem cells. These three pluripotency factors contribute to a complex molecular network that regulates a number of genes controlling pluripotency.<unk>  binds to DNA cooperatively with Oct4 at non-palindromic sequences to activate transcription of key pluripotency factors. Surprisingly, regulation of Oct4-Sox2 enhancers can occur without<unk> , likely due to expression of other Sox proteins. However, a group of researchers concluded that the primary role of<unk>  in embryonic stem cells is controlling Oct4 expression, and they both perpetuate their own expression when expressed concurrently. In an experiment involving mouse embryonic stem cells, it was discovered that<unk>  in conjunction with Oct4, c-Myc and Klf4 were sufficient for producing induced pluripotent stem cells. 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<unk>  and Oct4 binding sites in male germ cells and post-transcriptional suppression of<unk>  by miR134. Varying levels of<unk>  affect embryonic stem cells' fate of differentiation.<unk>  inhibits differentiation into the mesendoderm germ layer and promotes differentiation into neural ectoderm germ layer. Npm1/Sox2 complexes are sustained when differentiation is induced along the ectodermal lineage, emphasizing an important functional role for<unk>  in ectodermal differentiation. A study conducted in Milano, Italy showed, through the development of a knockout model, that deficiency of<unk>  results in neural malformities and eventually fetal death, further underlining<unk> 's vital role in embryonic development. Neural stem cells In neurogenesis,<unk>  is expressed throughout developing cells in the neural tube as well as in proliferating central nervous system progenitors. However,<unk>  is downregulated during progenitors' final cell cycle during differentiation when they become post mitotic. Cells expressing<unk>  are capable of both producing cells identical to themselves and differentiated neural cell types, two necessary hallmarks of stem cells. Thus signals controlling<unk>  expression in the presumptive neuronal compartment, like Notch signaling, control what size the neuronal compartment finally reaches. Proliferation of<unk> + neural stem cells can generate neural precursors as well as<unk> + neural stem cell population. Differences in brain size between the species thus relate to the capacity of different species to maintain<unk>  expression in the developing neural systems. 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<unk>  in the developing neural system. Induced pluripotency is possible using adult neural stem cells, which express higher levels of<unk>  and c-Myc than embryonic stem cells. Therefore, only two exogenous factors, one of which is necessarily Oct4, are sufficient for inducing pluripotent cells from neural stem cells, lessening the complications and risks associated with introducing multiple factors to induce pluripotency. Eye deformities Mutations in this gene have been linked with bilateral anophthalmia, a severe structural eye deformity. Cancer In lung development,<unk>  controls the branching morphogenesis of the bronchial tree and differentiation of the epithelium of airways. Overexpression causes an increase in neuroendocrine, gastric/intestinal and basal cells. Under normal conditions,<unk>  is critical for maintaining self-renewal and appropriate proportion of basal cells in adult tracheal epithelium. However, its overexpression gives rise to extensive epithelial hyperplasia and eventually carcinoma in both developing and adult mouse lungs. In squamous cell carcinoma, gene amplifications frequently target the 3q26.3 region. The gene for<unk>  lies within this region, which effectively characterizes<unk>  as an oncogene, although in adenocarcinoma of the esophagus loss of<unk>  is strongly associated with worse prognosis, effectively characterising<unk>  as a tumor suppressor. It thus fair to say that the function of<unk>  in cancer is pleiotropic.<unk>  is a key upregulated factor in lung squamous cell carcinoma, directing many genes involved in tumor progression.<unk>  overexpression cooperates with loss of Lkb1 expression to promote squamous cell lung cancer in mice. Its overexpression also activates cellular migration and anchorage-independent growth.<unk>  expression is also found in high gleason grade prostate cancer, and promotes castration-resistant prostate cancer growth. The ectopic expression of<unk>  may be related to abnormal differentiation of colorectal cancer cells.<unk>  has been shown to be relevant in the development of Tamoxifen resistance in breast cancer. In Glioblastoma multiforme,<unk>  is a well-established stem cell transcription factor needed to induce and maintain stemness properties of glioblastoma cancer cells.
SOX2
TFM-4AS-1
CDK13
FOXP3
SPATA16
CoWIN
ERCC2
WRAP53