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NANOG The secret to immortality

NANOG The secret to immortality. Ka Yi, Ling Genetics 677 04/28/09. Overview. Pluripotency All about Nanog Gene decoding Protein translation Nanog web Future directions. Image from http://www.cartoonstock.com/newscartoons/cartoonists/ato/lowres/aton305l.jpg. Star of immortality.

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NANOG The secret to immortality

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  1. NANOGThe secret to immortality Ka Yi, Ling Genetics 677 04/28/09

  2. Overview • Pluripotency • All about Nanog • Gene decoding • Protein translation • Nanog web • Future directions Image from http://www.cartoonstock.com/newscartoons/cartoonists/ato/lowres/aton305l.jpg

  3. Star of immortality 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) Image obtained from Takahashi et al. (2007),

  4. What’s the Nanog deal? • Pluripotent marker • Reprogramming factor Image from: http://www.savagechickens.com/images/chickengoal.jpg

  5. 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=61857and Lensch M. W. & Sullivan S. The cycle of developmental potency. Abcam(2008)

  6. What is pluripotency?

  7. Pluripotency Pluripotent Multi-potent

  8. Potency Eg. ES cells, iPS cells Eg. Adult stem cells

  9. Forever Young Image obtained from http://ific.uv.es/~lopes/pictures/kukuxumusu.jpg

  10. The Promise of Stem Cell Research Understanding Developmental Biology Regenerative Medicine Drug development Modified from http://www.csa.com/discoveryguides/stemcell/images/pluri.jpg

  11. How to induce pluripotent cells Lin28 Oct4 Nanog Sox2 Figure from: http://graphics8.nytimes.com/images/2007/06/06/science/0607-nat-webCELL.gif

  12. Necessary but not Sufficient Image obtained fromTakahashi (2007) DOI 10.1016/j.cell.2007.11.019

  13. 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

  14. Learning lessons Image from http://www.chrismadden.co.uk/genetics/dna-music.gif

  15. Nanog signaling Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency

  16. Multi-ome approach DNA Genome Messenger RNA Transcriptome Protein Proteome Image from: http://innovech.files.wordpress.com/2007/11/genome3.jpg

  17. 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

  18. Fitting the pieces Figure from http://www.ittc.ku.edu/bioinfo_seminar/images/wheel.gif

  19. 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=Nanogl

  20. DNA motifs What: Sex-determining region Y gene product (SRY) Consensus: AAACWAM Number of hits (Score above 99): 6What: 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/

  21. 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/

  22. 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

  23. NANOG protein crystals FASTA number: NP_079141UniProtKB : Q9H9SOLength of protein: 305 aaSubcellular location: Nucleus Image obtained from STRING, http://string.embl.de/newstring_cgi/show_network_section.pl

  24. Nanog (Mus muculus) Image obtained from NCBI MMDB, http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=61857

  25. 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=cl00084

  26. Nanog signaling Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency

  27. How does Nanog work?

  28. Phosphorylation Image obtained from NetPhos 2.0 Server, http://www.cbs.dtu.dk/cgi-bin/nph-webface?jobid=netphos,49DE647502FAC760&opt=none

  29. Dimerization

  30. Drawing analogies

  31. 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.jpg

  32. Nanog in other organisms Image obtained from NCBI Homologene, http://www.ncbi.nlm.nih.gov/sites/entrez

  33. 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)

  34. TreeFAM relations Image from Treefamilies database, http://www.treefam.org/cgi-bin/TFinfo.pl?ac=TF337402

  35. Comparing NANOG orthologues Homo sapiens Mus muculus Image from STRING, http://string.embl.de/newstring_cgi/show_network_section.pl

  36. 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

  37. Nanog Paralogues Image obtained from GeneCard, http://www.genecards.org/cgi-bin/cardsearch.pl#results

  38. 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

  39. 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

  40. Pseudo Nanog related to cancer?

  41. Inside view of crazy NANOG Image taken from Siu et al.(2008)  DOI: 10.2353/ajpath.2008.080288

  42. Inside view of looney NANOG Image taken from Introduction to Reproductive Biology. http://www.sgul.ac.uk/depts/immunology/~dash/troph/trophoblast.jpg

  43. 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

  44. Moving on Image from http://grandtextauto.org/archives/newyorker.jpg

  45. 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

  46. Fitting the pieces Figure from http://www.ittc.ku.edu/bioinfo_seminar/images/wheel.gif

  47. GTD detection Image from http://www.mchumor.com/00images/6575_biology_cartoon.gif

  48. 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.jpg

  49. Cures for tomorrow Image from: http://gen677.weebly.com/uploads/8/6/5/7/865764/28942.jpg

  50. Acknowledgements Thank you: Ahna for her kind help and guidance; Genetics 677 for the kind peer feedbacks and Jamie for the inspirational research!

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