User:Rehab.Gharawi/sandbox

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Lead[edit]

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[edit]

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.[1] 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.[2]

Function[edit]

Transcription programs in embryonic stem cells

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 SOX2to 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.[3]


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.[4]

POU5F1, TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 are also related genes all responsible for self-renewal and pluripotent differentiation.[5]

The NANOG protein has been found to be a transcriptional activator for the Rex1promoter, playing a key role in sustaining Rex1expression. Knockdown of NANOG in embryonic stem cellsresults in a reduction of Rex1expression, while forced expression of NANOG stimulates Rex1expression.[6]

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.[7][8][9][10][11]

Clinical significance[edit]

Cancer[edit]

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.[12][13][14]

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.[15]

Diagnostics[edit]

NANOG p8 gene has been evaluated as a prognostic and predictive cancer biomarker.[16]

Cancer Stem Cells[edit]

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.[17]

Evolution[edit]

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.[18] all in the same places: one duplication pseudogene and nine retropseudogenes. Of the nine shared NANOG retropseudogenes, two lack the poly-(A) tailscharacteristic 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 biologistspoint to NANOG and its pseudogenes as providing formidable evidence of common descentbetween humans and chimpanzees.[19]



Name[edit]

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[20][21]

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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  1. ^ Gawlik-Rzemieniewska, Natalia; Bednarek, Ilona (2015-11-30). "The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells". Cancer Biology & Therapy. 17 (1): 1–10. doi:10.1080/15384047.2015.1121348. ISSN 1538-4047. PMC 4848008. PMID 26618281.{{cite journal}}: CS1 maint: PMC format (link)
  2. ^ Zhang, Wei; Sui, Yi; Ni, Jun; Yang, Tao (2016). "Insights into the Nanog gene: A propeller for stemness in primitive stem cells". International Journal of Biological Sciences. 12 (11): 1372–1381. doi:10.7150/ijbs.16349. ISSN 1449-2288. PMC 5118783. PMID 27877089.{{cite journal}}: CS1 maint: PMC format (link)
  3. ^ GILBERT, SCOTT (2014). Developmental Biology. Sinauer Associates, Inc.
  4. ^ Zhang X, Stojkovic P, Przyborski S, Cooke M, Armstrong L, Lako M, Stojkovic M (Dec 2006). "Derivation of human embryonic stem cells from developing and arrested embryos". Stem Cells. 24 (12): 2669–76. doi:10.1634/stemcells.2006-0377. PMID 16990582.
  5. ^ Li SS, Liu YH, Tseng CN, Chung TL, Lee TY, Singh S (Aug 2006). "Characterization and gene expression profiling of five new human embryonic stem cell lines derived in Taiwan". Stem Cells and Development. 15 (4): 532–55. doi:10.1089/scd.2006.15.532. PMID 16978057.
  6. ^ Shi W, Wang H, Pan G, Geng Y, Guo Y, Pei D (Aug 2006). "Regulation of the pluripotency marker Rex-1 by Nanog and Sox2". The Journal of Biological Chemistry. 281 (33): 23319–25. doi:10.1074/jbc.M601811200. PMID 16714766.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ Shahini A, Choudhury D, Asmani M, Zhao R, Lei P, Andreadis S (Jan 2018). "NANOG restores the impaired myogenic differentiation potential of skeletal myoblasts after multiple population doublings". Stem Cell Research. 26: 55–66. doi:10.1016/j.scr.2017.11.018. PMID 29245050.
  8. ^ Shahini A, Mistriotis P, Asmani M, Zhao R, Andreadis S (Jun 2017). "NANOG Restores Contractility of Mesenchymal Stem Cell-Based Senescent Microtissues". Tissue Eng Part A. 23 (11–12): 535–545. doi:10.1089/ten.TEA.2016.0494. PMID 28125933.
  9. ^ Mistriotis P, Bajpai V, Wang X, Rong N, Shahini A, Asmani M, Liang M, Wang J, Lei P, Liu S, Zhao R, Andreadis S (Jan 2017). "NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression". Stem Cells. 35 (1): 207–221. doi:10.1002/stem.2452. PMID 27350449.
  10. ^ Han J, Mistriotis P, Lei P, Wang D, Liu S, Zhao R, Andreadis S (Dec 2012). "Nanog Reverses the Effects of Organismal Aging on Mesenchymal Stem Cell Proliferation and Myogenic Differentiation Potential". Stem Cells. 30 (12): 2746–2759. doi:10.1002/stem.1223. PMC 3508087. PMID 22949105.
  11. ^ Munst B, Thier M, Winnemoller D, Helfen M, Thummer R, Edenhofer F (Jan 2016). "Nanog induces suppression of senescence through downregulation of p27KIP1 expression". Journal of Cell Science. 129 (5): 912–20. doi:10.1242/jcs.167932. PMC 4813312. PMID 26795560.{{cite journal}}: CS1 maint: extra punctuation (link)
  12. ^ Gong S, Li Q, Jeter CR, Fan Q, Tang DG, Liu B (2015). "Regulation of NANOG in cancer cells". Molecular Carcinogenesis. 54 (9): 679–87. doi:10.1002/mc.22340. PMC 4536084. PMID 26013997.
  13. ^ Jeter CR, Yang T, Wang J, Chao HP, Tang DG (2015). "Concise Review: NANOG in Cancer Stem Cells and Tumor Development: An Update and Outstanding Questions". Stem Cells (Dayton, Ohio). 33 (8): 2381–90. doi:10.1002/stem.2007. PMC 4509798. PMID 25821200.
  14. ^ Gawlik-Rzemieniewska N, Bednarek I (2016). "The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells". Cancer Biology & Therapy. 17 (1): 1–10. doi:10.1080/15384047.2015.1121348. PMC 4848008. PMID 26618281.
  15. ^ Zhang, Wei; Sui, Yi; Ni, Jun; Yang, Tao (2016). "Insights into the Nanog gene: A propeller for stemness in primitive stem cells". International Journal of Biological Sciences. 12 (11): 1372–1381. doi:10.7150/ijbs.16349. ISSN 1449-2288. PMC 5118783. PMID 27877089.{{cite journal}}: CS1 maint: PMC format (link)
  16. ^ Iv Santaliz-Ruiz LE, Xie X, Old M, Teknos TN, Pan Q (2014). "Emerging role of nanog in tumorigenesis and cancer stem cells". International Journal of Cancer. 135 (12): 2741–8. doi:10.1002/ijc.28690. PMC 4065638. PMID 24375318.
  17. ^ Zhang, Wei; Sui, Yi; Ni, Jun; Yang, Tao (2016). "Insights into the Nanog gene: A propeller for stemness in primitive stem cells". International Journal of Biological Sciences. 12 (11): 1372–1381. doi:10.7150/ijbs.16349. ISSN 1449-2288. PMC 5118783. PMID 27877089.{{cite journal}}: CS1 maint: PMC format (link)
  18. ^ Gawlik-Rzemieniewska, Natalia; Bednarek, Ilona (2015-11-30). "The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells". Cancer Biology & Therapy. 17 (1): 1–10. doi:10.1080/15384047.2015.1121348. ISSN 1538-4047. PMC 4848008. PMID 26618281.{{cite journal}}: CS1 maint: PMC format (link)
  19. ^ Daniel J. Fairbanks (2007). Relics of Eden: The Powerful Evidence of Evolution in Human DNA. Buffalo, N.Y: Prometheus Books. pp. 94–96, 177–182. ISBN 1-59102-564-8.
  20. ^ "ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth". Retrieved 2007-07-26.
  21. ^ Gawlik-Rzemieniewska, Natalia; Bednarek, Ilona (2015-11-30). "The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells". Cancer Biology & Therapy. 17 (1): 1–10. doi:10.1080/15384047.2015.1121348. ISSN 1538-4047. PMC 4848008. PMID 26618281.{{cite journal}}: CS1 maint: PMC format (link)
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