Wealth of genomic hotspots discovered in embryonic stem cells
Should advance understanding of cell reprogramming, renewal and
pluripotency
In a paper published in Cell on June 13, 2008, Singapore scientists
at the Genome Institute of Singapore (GIS) and the National
University of Singapore (NUS) unveil an atlas that showing the
location of "genomic hotspots" of essential protein "switches"
(transcription factors) that are critical for maintaining the
embryonic stem (ES) cell state.
Using advanced high throughput sequencing technology, the scientists
discovered over 3,000 hotspots. These findings could improve
understanding of the unique properties of stem cells that enable them
to maintain their intriguing ability to grow and differentiate to
virtually any cell type.
"This is the first time such a large scale study has been conducted
in Singapore and obtaining such groundbreaking results has caused
much excitement," said Wei Chia Lin, Ph.D., Senior Group Leader at
GIS. "This blueprint that we obtained is like a treasure map,
pointing us to specific sites where we can further study how these
switches interact within the cell. Hopefully, this will eventually
allow us unlock the secrets of stem cells."
Ng Huck Hui, Ph.D., also a Senior Group Leader at GIS, added, "we
think that these 'stemness' hotspots are the most critical points in
the genetic blueprint of ES cells. By targeting these hotspots, we
may be able to reconnect the wiring in non-stem cells and jump-start
the stem cell program in them. This can potentially create an
inexhaustible source of clinically useful cells for regenerative
medicine or cell based therapies in the future." The team has already
started work to investigate further into this area of research.
"Using cutting edge sequencing technology, scientists from the GIS
and NUS have identified hotspots in embryonic stem cells," said Prof.
Lee Eng Hin, Executive Director of A*STAR's Biomedical Research
Council. "These are important hubs of the genome of embryonic stem
cells. This piece of work illustrates how scientists from different
disciplines and across institutions can come together to define
fundamental features of these intriguing cells."
"In this new paper in Cell, the team at the GIS continues their
remarkable progress in defining the precise DNA sequences to which an
important group of 13 transcriptional factors bind in mouse embryonic
stem cells," said Alan Colman, Ph.D., Executive Director of
Singapore's Stem Cell Consortium. "This particular group of factors
is responsible for maintaining the self renewal and pluripotency of
the embryonic stem cells. The team shows that many of the factors
which bind to the same gene regions ('hotspots') and their work
provide a working model of the transcriptional networks at play
within the cells, and how these intracellular networks are linked to
events that can be influenced by external stimuli."
The researchers performed genome-wide mapping of the in vivo binding
sites for 13 sequence-specific transcription factors in ES cells.
These transcription factors play different roles in self-renewal,
pluripotency, reprogramming and chromatin insulation. This study
uncovers two major modes of binding that give rise to transcription
factor co- localization hotspots. The Nanog/Oct4/Sox2 centric
hotspots are commonly co-bound by Smad1 and STAT3 and they represent
points of integration for the intrinsic and external signaling
pathways. The combinatorial wiring of transcription factors is
important in deciphering the code behind gene expression program in
ES cells.
###
The work done by the GIS team is a follow up on a series of ongoing
research ( "The Oct4 and Nanog transcription network that regulates
pluripotency in mouse embroynic stem cells," Nature Genetics 38:431-
440, 2006) into understanding and mapping the transcriptional
networks of master genes in ES and somatic cells.
Notes to editor:
Research publication:
The research findings described in the press release are reported in
the June 13, 2008 CELL paper, "Integration of external signaling
pathways with the core transcriptional network in embryonic stem
cells".
About the Genome Institute of Singapore www.gis.a-star.
The Genome Institute of Singapore (GIS) is a member of the Agency for
Science, Technology and Research (A*STAR). It is a national
initiative with a global vision that seeks to use genomic sciences to
improve public health and public prosperity. Established in 2001 as a
centre for genomic discovery, the GIS will pursue the integration of
technology, genetics and biology towards the goal of individualized
medicine. The key research areas at the GIS include systems biology,
stem cell & developmental biology, cancer biology & pharmacology,
human genetics, infectious diseases, genomic technologies, and
computational & mathematical biology. The genomics infrastructure at
the GIS is utilized to train new scientific talent, to function as a
bridge for academic and industrial research, and to explore
scientific questions of high impact.
About the Agency for Science, Technology and Research www.a-
star.edu.sg
The Agency for Science, Technology and Research, or A*STAR, is
Singapore's lead agency for fostering world-class scientific research
and talent for a vibrant knowledge- based Singapore. A*STAR actively
nurtures public sector research and development in Biomedical
Sciences, Physical Sciences and Engineering, with a particular focus
on fields essential to Singapore's manufacturing industry and new
growth industries. It oversees 14 research institutes and supports
extramural research with the universities, hospital research centres
and other local and international partners. At the heart of this
knowledge intensive work is human capital. Top local and
international scientific talent drive knowledge creation at A*STAR
research institutes. The agency also sends scholars for
undergraduate, graduate and post-doctoral training in the best
universities, a reflection of the high priority A*STAR places on
nurturing the next generation of scientific talent.
For enquiries, please contact the following:
In Singapore:
Winnie Serah Lim
Tel: (65) 6478 8013
(65) 9730 7884
Email: limcp2@gis.a-
Joshua Woo
Tel: (65) 6586 9771
Email: Joshua_woo@a-
In U.S.:
Cathy Yarbrough
Tel: 858-243-1814
Email: sciencematter@
Public release date: 13-Jun-2008
[ Print Article | E-mail Article | Close Window ]
Contact: Cathy Yarbrough
sciencematter@
858-243-1814
Agency for Science, Technology and Research (A*STAR), Singapore
http://www.eurekale
http://www.medindia
Cells-Found-
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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