User:Rehab.Gharawi/sandbox

Lead
Homeobox protein NANOG is a transcriptional factor that help Embryonic Stem cells maintain the pluripotency, ‘an undifferentiation state’, by suppressing cell determination factors. Therefore NANOG deletion will trigger differentiation of ES cells. There are many different types of cancer that are associated with NANOG.

Structure
The Human NANOG protein coded by the NANOG1 gene, consist of 305 amino acids and possesses 3 functional domains: the N-terminal domain, the C- terminal domain, and the conserved homeodomain motif. The homeodomain region facilitates DNA binding. The Human Nanog 1 gene is localized on chromosome 12, and the mRNA contains a 915 bp open reading frame(ORF) with 4 exons and 3 introns. The N-terminal region of human NANOG is rich in Ser, Thr and Pro residues, and the C-terminus contains tryptophan-rich domain. The homeodomain in hNANOG ranges from residues 95 to 155.There are also additional NANOG genes (NANOG2, NANOG p8) which potentially effect ESCs differentiation. Scientist have shown that NANOG1 is fundamental for self-renewal and pluripotency and NONAG p8 is highly expressed in cancer cells.

Function
NANOG is a transcription factor in embryonic stem cells(ESCs) and is thought to be a key factor in maintaining pluripotency. NANOG is thought to function in concert with other factors such as POU5F1 (Oct-4) and SOX2 to establish ESC identity. These cells offer an important area of study because of their ability to maintain pluripotency. In other words, these cells have the ability to become virtually any cell of any of the three germ layers (endoderm, ectoderm, mesoderm). It is for this reason that understanding the mechanisms that maintain a cell's pluripotency is critical for researchers to understand how stem cells work; and may lead to future advances in treating degenerative diseases.

Analysis of arrested embryos demonstrated that embryos express pluripotency marker genes such as POU5F1, NANOG and Rex1. Derived human ESC lines also expressed specific pluripotency markers:


 * TRA-1-60
 * TRA-1-81
 * SSEA4
 * alkaline phosphatase
 * TERT
 * Rex1

These markers allowed for the differentiation in vitro and in vivo conditions into derivatives of all three germ layers.

POU5F1, TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 are also related genes all responsible for self-renewal and pluripotent differentiation.

The NANOG protein has been found to be a transcriptional activator for the Rex1 promoter, playing a key role in sustaining Rex1 expression. Knockdown of NANOG in embryonic stem cells results in a reduction of Rex1 expression, while forced expression of NANOG stimulates Rex1 expression.

Besides the effects of NANOG in the embryonic stages of life, ectopic expression of NANOG in the adult stem cells can restore the proliferation and differentiation potential that is lost due to organismal aging or cellular senescence.

Cancer
NANOG is highly expressed in cancer stem cells and may thus function as an oncogene to promote carcinogenesis. High expression of NANOG correlates with poor survival in cancer patients.

Recent researches has shown that the localization of NANOG and other transcription factors have potential consequences on cellular function. Experimental evidence has shown that the level of NANOG p8 expression is elevated specially in cancer cells, which mean that NANOG p8 gene is a critical member in (CSCs) Cancer stem cells, so knocking it down could reduce the cancer malignancy.

Diagnostics
NANOG p8 gene has been evaluated as a prognostic and predictive cancer biomarker.

Cancer Stem Cells
Cancer stem cells (CSCs) are a subpopulation of cancer cells that possess stemness properties which include self-renew, differentiate, and proliferative potential. Also, this property could enable CSCs to regrow tumors and cause metastasis. So, experimental evidence indicates that stemness properties disappear during the differentiation stage.

Evolution
Humans and chimpanzees share ten NANOG pseudogenes (NanogP2-P11) during evaluation, two of them are located on the X chromosome and they characterized by the 5’ promoter sequences and the absence of introns as a result of mRNA retrotransposition. all in the same places: one duplication pseudogene and nine retropseudogenes. Of the nine shared NANOG retropseudogenes, two lack the poly-(A) tails characteristic of most retropseudogenes, indicating copying errors occurred during their creation. Due to the high improbability that the same pseudogenes (copying errors included) would exist in the same places in two unrelated genomes, evolutionary biologists point to NANOG and its pseudogenes as providing formidable evidence of common descent between humans and chimpanzees.

Name
Professor Ian Chambers (currently of the MRC Centre for Regenerative Medicine, The University of Edinburgh, UK) who isolated the mouse Nanog gene said: "Nanog seems to be a master gene that makes embryonic stem cells grow in the laboratory. In effect this makes stem cells immortal. The name NANOG derives from Tír na nÓg legend."the mythical Celtic land of youth I read an article about Stem cell and I really liked it. Actually, I read something that make me wondering! why the males have more adult stem cells in the bone morrow than the females during the reproductive years? I will search and I hope to find an answer.

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