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NANOG The secret to immortality Ka Yi, Ling Genetics 677 04/28/09
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Overview Pluripotency All about Nanog Gene decoding Protein translation Nanog web Future directions Image from http://www.cartoonstock.com/newscarto ons/cartoonists/ato/lowres/aton305l.jpg
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Star of immortality Image obtained from Takahashi et al. (2007), Image obtained fromTakahashi et al. (2007) DOI 10.1016/j.cell.2007.11.019 and Lensch M. W. & Sullivan S. The cycle of developmental potency. Abcam(2008)
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What’s the Nanog deal? 1)Pluripotent marker 2)Reprogramming factor Image from: http://www.savagechickens.com/images/chickengoal.jpghttp://www.savagechickens.com/images/chickengoal.jpg
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Deciphering Nanog Image obtained fromHyslop et al. (2005) Stem Cells 2005;23:1035–1043, NCBI MMDB, http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=61857 and Lensch M. W. & Sullivan S. The cycle of developmental potency. Abcam(2008)
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What is pluripotency?
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Pluripotency Pluripotent Multi- potent
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PotencyPotencyPotencyPotency Eg. ES cells, iPS cells Eg. Adult stem cells
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Forever Young Image obtained from http://ific.uv.es/~lopes/pictures/kukuxumusu.jpg
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Modified from http://www.csa.com/discoveryguides/stemcell/images/pluri.jpg The Promise of Stem Cell Research Understanding Developmental Biology Regenerative Medicine Drug development
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How to induce pluripotent cells Figure from: http://graphics8.nytimes.com/images/2007/06/06/science/0607-nat-webCELL.gif Nanog Sox2 Oct4 Lin28
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Necessary but not Sufficient Image obtained fromTakahashi (2007) DOI 10.1016/j.cell.2007.11.019
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Goal: To learn the mechanisms of Nanog function Nanog Image modified from http://i1.iofferphoto.com/img/item/489/760/11/discover_how_stuff_works.jpg
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Learning lessons Image from http://www.chrismadden.co.uk/genetics/dna-music.gif
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Nanog signaling Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency
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Multi-ome approach Image from: http://innovech.files.wordpress.com/2007/11/genome3.jpg DNA Messenger RNA Protein Genome Transcriptome Proteome
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Image modified from Stein (2001) and the Human Proteome Initiative. (2007) http://ca.expasy.org/sprot/hpi/hpi_desc.html Retrieved March 24, 2009. and courtesy of Eva and Jessica’s Gen677 presentation
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Fitting the pieces Figure from http://www.ittc.ku.edu/bioinfo_seminar/images/wheel.gif
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Chromosome hunting GeneID: 79923 Size: 6661 base pairs Chromosome: 12 Location: 12p13.31 Image obtained from GeneCards, http://www.genecards.org/cgi-bin/carddisp.pl?gene=NANOG&search=Nanoglhttp://www.genecards.org/cgi-bin/carddisp.pl?gene=NANOG&search=Nanogl
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DNA motifs What: Sex-determining region Y gene product (SRY) Consensus: AAACWAM Number of hits (Score above 99): 6 What: Homeo domain factor (Nkx-2.5/Csx), tinman homolog Consensus: TYAAGTG Number of hits (Score above 99): 7 Image obtained from Kyoto University Bioinformatics Centre, http://motif.genome.jp/http://motif.genome.jp/
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DNA motifs What: CAP signal, transcription initiation Consensus: NCANNNNN Number of hits (Score above 99): 2 What: GATA binding factor-1 Consensus: SNNGATNNNN Number of hits (Score above 99): - (Score above 90): 12 Image obtained from Kyoto University Bioinformatics Centre, http://motif.genome.jp/http://motif.genome.jp/
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Nanog: DNA level Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency
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NANOG protein crystals Image obtained from STRING, http://string.embl.de/newstring_cgi/show_network_section.plhttp://string.embl.de/newstring_cgi/show_network_section.pl FASTA number: NP_079141 UniProtKB : Q9H9SO Length of protein: 305 aa Subcellular location: NucleusQ9H9SO
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Nanog (Mus muculus) Image obtained from NCBI MMDB, http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=61857
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Homeobox domain Pfam, SMART and prosite – similar predictions Image from Prosite, http://www.expasy.ch/cgi-bin/prosite/ScanView.cgi?scanfile=89996073962.scan.gz and NCBI conserved domains, http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cl00084http://www.expasy.ch/cgi-bin/prosite/ScanView.cgi?scanfile=89996073962.scan.gzhttp://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cl00084
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Nanog signaling Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency
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How does Nanog work?
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Phosphorylation Image obtained from NetPhos 2.0 Server, http://www.cbs.dtu.dk/cgi-bin/nph-webface?jobid=netphos,49DE647502FAC760&opt=none
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Dimerization
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Drawing analogies
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Animal stars Image from: http://www.socialfiction.org/img/Enlarged_c_elegans.PNG, http://brembs.net/learning/drosophila/fly_down.jpg, http://64.207.144.142/movabletype/PETA2Daily/archives/kick1.PNG and http://images.forbes.com/images/2001/07/26/mice_400x300.jpghttp://www.socialfiction.org/img/Enlarged_c_elegans.PNG http://brembs.net/learning/drosophila/fly_down.jpghttp://64.207.144.142/movabletype/PETA2Daily/archives/kick1.PNG
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Nanog in other organisms Image obtained from NCBI Homologene, http://www.ncbi.nlm.nih.gov/sites/entrez
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Phylogeny tree – Closeness of Nanog Image from Deereeper A. et al. Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W465-9. Epub 2008 Apr 19. (PubMed)
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TreeFAM relations Image from Treefamilies database, http://www.treefam.org/cgi-bin/TFinfo.pl?ac=TF337402
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Comparing NANOG orthologues Homo sapiensMus muculus Image from STRING, http://string.embl.de/newstring_cgi/show_network_section.pl http://string.embl.de/newstring_cgi/show_network_section.pl
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Protein friends of Nanog Table obtained from Lewitzky. M and Yamanaka S. (2007) Reprogramming somatic cells towards pluripotency by defined factors. Current Opinion in Biotechnology. 18: 467-473
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Nanog Paralogues Image obtained from GeneCard, http://www.genecards.org/cgi-bin/cardsearch.pl#results
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Mutant phenotypes Jaenisch paper Table obtained from Boyer, L. A., Mathur, D. and Jaenisch R. (2006) Molecular control of pluripotency. Current Opinion in Genetics & Development. 16, 455-462
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Nanog: protein level Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency
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Pseudo Nanog related to cancer?
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Inside view of crazy NANOG Image taken from Siu et al.(2008) DOI: 10.2353/ajpath.2008.080288
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Inside view of looney NANOG Image taken from Introduction to Reproductive Biology. http://www.sgul.ac.uk/depts/immunology/~dash/troph/trophoblast.jpg http://www.sgul.ac.uk/depts/immunology/~dash/troph/trophoblast.jpg
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NANOG gone looney Image from SonoWorld (2009) Complete Molar Gestation: Role of Ultrasound, http://www.sonoworld.com/Article/ShowArticleImage.aspx?id=9098&Type=Paragraph and Mchumor, http://www.pioneer.net/~mchumor/00images/2192_pregnancy_cartoon.gif http://www.sonoworld.com/Article/ShowArticleImage.aspx?id=9098&Type=Paragraphhttp://www.pioneer.net/~mchumor/00images/2192_pregnancy_cartoon.gif
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Moving on Image from http://grandtextauto.org/archives/newyorker.jpg
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Image modified from Stein (2001) and the Human Proteome Initiative. (2007) http://ca.expasy.org/sprot/hpi/hpi_desc.html Retrieved March 24, 2009. and courtesy of Eva and Jessica’s Gen677 presentation
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Fitting the pieces Figure from http://www.ittc.ku.edu/bioinfo_seminar/images/wheel.gif
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GTD detection Image from http://www.mchumor.com/00images/6575_biology_cartoon.gif
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Confirmation assays Function analysis Nanog dimer Phosphorylation Global outlook Chemical genetics Transcriptome sequencing Reprogramming Image modified from http://dcad.com.pl/image/dna1.jpg, http://www.dnastar.com/media/linegraphLrg.jpg and http://www.cs.usyd.edu.au/%7Eirena/arrayimage.jpghttp://dcad.com.pl/image/dna1.jpghttp://www.dnastar.com/media/linegraphLrg.jpg http://www.cs.usyd.edu.au/%7Eirena/arrayimage.jpg
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Cures for tomorrow Image from: http://gen677.weebly.com/uploads/8/6/5/7/865764/28942.jpg
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Acknowledgements Thank you:Ahna for her kind help and guidance; Genetics 677 for the kind peer feedbacks andJamie for the inspirational research!
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Thank you! Any questions? Image from http://www.newslettercartoons.com/freedaily/5651_todayT.gif and http://www.media-freaks.com/work/leilei/peterpan/peterpan-02.jpghttp://www.newslettercartoons.com/freedaily/5651_todayT.gif http://www.media-freaks.com/work/leilei/peterpan/peterpan-02.jpg
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