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Overview
Pluripotency
All about NanogGene decodingProtein translationNanog web
Future directions Image from http://www.cartoonstock.com/newscartoons/cartoonists/ato/lowres/aton305l.jpg
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)
What’s the Nanog deal?
1)Pluripotent marker
2)Reprogramming factor
Image from: http://www.savagechickens.com/images/chickengoal.jpg
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)
Modified from http://www.csa.com/discoveryguides/stemcell/images/pluri.jpg
The Promise of Stem Cell Research
UnderstandingDevelopmenta
l Biology
Regenerative Medicine
Drug development
How to induce pluripotent cells
Figure from: http://graphics8.nytimes.com/images/2007/06/06/science/0607-nat-webCELL.gif
Nanog Sox2
Oct4Lin28
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
Nanog signaling
Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency
Multi-ome approach
Image from: http://innovech.files.wordpress.com/2007/11/genome3.jpg
DNA
Messenger RNA
Protein
Genome
Transcriptome
Proteome
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
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
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/
DNA motifs
What: CAP signal, transcription initiation Consensus: NCANNNNN Number of hits (Score above 99): 2
What: GATA binding factor-1 Consensus: SNNGATNNNNNumber of hits (Score above 99): -
(Score above 90): 12
Image obtained from Kyoto University Bioinformatics Centre, http://motif.genome.jp/
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
NANOG protein crystals
Image obtained from STRING, http://string.embl.de/newstring_cgi/show_network_section.pl
FASTA number: NP_079141UniProtKB : Q9H9SOLength of protein: 305 aaSubcellular location: Nucleus
Nanog (Mus muculus)
Image obtained from NCBI MMDB, http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=61857
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
Nanog signaling
Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency
Phosphorylation
Image obtained from NetPhos 2.0 Server, http://www.cbs.dtu.dk/cgi-bin/nph-webface?jobid=netphos,49DE647502FAC760&opt=none
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
Nanog in other organisms
Image obtained from NCBI Homologene, http://www.ncbi.nlm.nih.gov/sites/entrez
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)
TreeFAM relations
Image from Treefamilies database, http://www.treefam.org/cgi-bin/TFinfo.pl?ac=TF337402
Comparing NANOG
orthologues
Homo sapiens Mus muculus
Image from STRING, http://string.embl.de/newstring_cgi/show_network_section.pl
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
Nanog Paralogues
Image obtained from GeneCard, http://www.genecards.org/cgi-bin/cardsearch.pl#results
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
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
Inside view of looney NANOG
Image taken from Introduction to Reproductive Biology. http://www.sgul.ac.uk/depts/immunology/~dash/troph/trophoblast.jpg
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
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
Confirmation assays
Function analysisNanog dimerPhosphorylation
Global outlookChemical geneticsTranscriptome sequencing
ReprogrammingImage 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
Acknowledgements
Thank you:Ahna
for her kind help and guidance;
Genetics 677 for the kind peer feedbacks and
Jamie for the inspirational research!
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.jpg