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4 Οκτ 2013 (πριν από 3 χρόνια και 10 μήνες)

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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 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)

What is
pluripotency
?


Pluripotency


Pluripotent

Multi
-
potent

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

Modified from http://
www.csa.com/discoveryguides/stemcell/images/pluri.jpg

The Promise of Stem Cell
Research

Understanding

Developmental
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

Oct4

Lin28

Necessary

but not

Sufficient

Image obtained fromTakahashi (2007)
DOI 10.1016/j.cell.2007.11.019

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

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

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

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

Image obtained from STRING,
http://string.embl.de/newstring_cgi/show_network_section.pl



FASTA number:
NP_079141

UniProtKB :
Q9H9SO

Length of protein:
305 aa

Subcellular 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


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