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Wealth of genomic hotspots discovered in embryonic stem cells
June 16, 2008Should 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.
Agency for Science, Technology and Research (A*STAR), Singapore
"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.
Agency for Science, Technology and Research (A*STAR), Singapore
Embryonic Stem Cells Current Events and Embryonic Stem Cells News RSSOf mice and men: Stem cells and ethical uncertainties
The recent creation of live mice from induced pluripotent stem cells (iPSCs) not only represents a remarkable scientific achievement, but also raises important issues, according to bioethicists at The Johns Hopkins University's Berman Institute of Bioethics.
NIH-funded researchers transform embryonic stem cells into human germ cells
Researchers funded in part by the National Institutes of Health have discovered how to transform human embryonic stem cells into germ cells, the embryonic cells that ultimately give rise to sperm and eggs.
Placental precursor stem cells require testosterone-free environment to survive
Trophoblast stem cells (TSCs), cells found in the layer of peripheral embryonic stem cells from which the placenta is formed, are thought to exhibit "immune privilege" that aids cell survivability and is potentially beneficial for cell and gene therapies.
Endocrine Society calls for expanded scope and funding for stem cell research
Stem cell research holds great promise for the treatment of millions of Americans with debilitating and possibly fatal diseases.
Small mechanical forces have big impact on embryonic stem cells
Applying a small mechanical force to embryonic stem cells could be a new way of coaxing them into a specific direction of differentiation, researchers at the University of Illinois report. Applications for force-directed cell differentiation include therapeutic cloning and regenerative medicine.
Fate Therapeutics announces creation of small molecule platform for commercial-scale reprogramming
Fate Therapeutics, Inc. announced today the generation of human induced-pluripotent stem cells (iPSCs) using a combination of small molecules that significantly improves the speed and efficiency of reprogramming.
A major step in making better stem cells from adult tissue
October 15, 2009 A team led by scientists from The Scripps Research Institute has developed a method that dramatically improves the efficiency of creating stem cells from human adult tissue, without the use of embryonic cells.
New strategy for mending broken hearts?
By mimicking the way embryonic stem cells develop into heart muscle in a lab, Duke University bioengineers believe they have taken an important first step toward growing a living "heart patch" to repair heart tissue damaged by disease.
Liver cells grown from patients' skin cells
Scientists at The Medical College of Wisconsin in Milwaukee have successfully produced liver cells from patients' skin cells opening the possibility of treating a wide range of diseases that affect liver function.
Major improvements made in engineering heart repair patches from stem cells
University of Washington (UW) researchers have succeeded in engineering human tissue patches free of some problems that have stymied stem-cell repair for damaged hearts.
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