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/newscarto
ons/cartoonists/ato/lowres/aton305l.jpg
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),
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)
What is pluripotency?
Pluripotency
Pluripotent
Multipotent
P
o
t
e
n
c
y
Eg. ES cells, iPS cells
Eg. Adult stem cells
Forever Young
Image obtained from http://ific.uv.es/~lopes/pictures/kukuxumusu.jpg
The Promise of Stem Cell
Research
Understanding
Developmental
Biology
Regenerative
Medicine
Drug
development
Modified from http://www.csa.com/discoveryguides/stemcell/images/pluri.jpg
How to induce
pluripotent cells
Lin28
Nanog
Oct4
Sox2
Figure from: http://graphics8.nytimes.com/images/2007/06/06/science/0607-nat-webCELL.gif
Necessary
but not
Sufficient
Image obtained fromTakahashi (2007)
DOI 10.1016/j.cell.2007.11.019
Nanog
Goal:
To learn the
mechanisms of
Nanog function
Image modified from http://i1.iofferphoto.com/img/item/489/760/11/discover_how_stuff_works.jpg
Learning lessons
Image from http://www.chrismadden.co.uk/genetics/dna-music.gif
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
DNA
Messenger
RNA
Protein
Genome
Transcriptome
Proteome
Image from: http://innovech.files.wordpress.com/2007/11/genome3.jpg
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
Fitting the pieces
Figure from http://www.ittc.ku.edu/bioinfo_seminar/images/wheel.gif
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: SNNGATNNNN
Number 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
FASTA number: NP_079141
UniProtKB : Q9H9SO
Length of protein: 305 aa
Subcellular location:
Nucleus
Image obtained from STRING, http://string.embl.de/newstring_cgi/show_network_section.pl
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
How does
Nanog
work?
Phosphorylation
Image obtained from NetPhos 2.0 Server,
http://www.cbs.dtu.dk/cgi-bin/nph-webface?jobid=netphos,49DE647502FAC760&opt=none
Dimerization
Drawing analogies
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
Pseudo Nanog related to
cancer?
Inside view of crazy
NANOG
Image taken from Siu et al.(2008) DOI: 10.2353/ajpath.2008.080288
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
Moving on
Image from http://grandtextauto.org/archives/newyorker.jpg
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
Fitting the pieces
Figure from http://www.ittc.ku.edu/bioinfo_seminar/images/wheel.gif
GTD detection
Image from http://www.mchumor.com/00images/6575_biology_cartoon.gif
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
Cures for tomorrow
Image from: http://gen677.weebly.com/uploads/8/6/5/7/865764/28942.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