Wealth of genomic hotspots discovered in embryonic stem cells

Jun 13, 2008

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.

Source: Agency for Science, Technology and Research (A*STAR)

Explore further: Researchers successfully clone adult human stem cells

add to favorites email to friend print save as pdf

Related Stories

Japan stem cell body splashes cash on luxury furniture

Apr 14, 2014

A publicly-funded research institute in Japan, already embattled after accusing one of its own stem cell scientists of faking data, has spent tens of thousands of dollars on designer Italian furniture, reportedly to use up ...

Recommended for you

Plants with dormant seeds give rise to more species

20 hours ago

Seeds that sprout as soon as they're planted may be good news for a garden. But wild plants need to be more careful. In the wild, a plant whose seeds sprouted at the first warm spell or rainy day would risk disaster. More ...

Researchers successfully clone adult human stem cells

Apr 18, 2014

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

User comments : 0

More news stories

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Plants with dormant seeds give rise to more species

Seeds that sprout as soon as they're planted may be good news for a garden. But wild plants need to be more careful. In the wild, a plant whose seeds sprouted at the first warm spell or rainy day would risk disaster. More ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.

Health care site flagged in Heartbleed review

People with accounts on the enrollment website for President Barack Obama's signature health care law are being told to change their passwords following an administration-wide review of the government's vulnerability to the ...

Impact glass stores biodata for millions of years

(Phys.org) —Bits of plant life encapsulated in molten glass by asteroid and comet impacts millions of years ago give geologists information about climate and life forms on the ancient Earth. Scientists ...