Scientists at the Genome Institute of Singapore (GIS) have recently generated significant single cell expression data crucial for a detailed molecular understanding of mammalian development from fertilization to embryo implantation, a process known as the preimplantation period. The knowledge gained has a direct impact on clinical applications in the areas of regenerative medicine and assisted reproduction.

This study, published in Developmental Cell on April 20, 2010, is the first of its kind to apply single cell gene expression analysis of many genes to hundreds of cells in a developmental system.

Using the new BioMark microfluidic technology and the mouse preimplantation embryo as a model, the scientists were able to study the expression of 48 genes from individual cells and applied this to analyze over 600 individual cells from the 1-cell to the 64-cell stage of preimplantation development. This high throughput single cell research methodology provides the scientists with the ability to detect dynamic patterns in cellular behaviour, which is unprecedented in the field. Significantly, the findings of the study resolves some of the arguments pertaining to cellular differentiation events and places fibroblast growth factor signalling as the primary event in the later cell fate decisions.

Executive Director at the GIS, a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), Professor Edison Liu said,

“This remarkable work by Guoji Guo, Mikael Huss, Paul Robson and colleagues uses new microgenomic technologies to map, over time, how a single cell decides to permanently become different parts of an embryo.  Within one division, cells commit to specific developmental lineages by expressing defined sets of genes.  This research now opens the possibility of assessing the genetic triggers for fate determination of individual cells in developmental time. On another level, this work highlights the importance of new microtechnologies in advancing the understanding of early embryonic events. “

Professor Davor Solter, Senior Principal Investigator of the Institute of Medical Biology, A*STAR, added, “This is a real technological tour de force. The authors investigated changes in expression of multiple genes on the single cell level during preimplantation mouse development. They clearly demonstrated gradual and stochastic lineage allocation and absence of predetermination. These results conclusively resolved one of the hotly debated issues in mammalian development and provided important new insight into the mechanism which regulates early development in mammals.”

“These are important findings.  The team at GIS provided a new look into the complex and little-understood process of early embryo development.  It also demonstrates the power of single cell gene expression.  It is clear that individual cells and small groups of cells behave differently than the aggregate population, and these differences are key to understanding the biology of the system as a whole.” said Gajus Worthington,  president and chief executive officer of Fluidigm.  “It always provides a special thrill when researchers use the capabilities of Fluidigm’s technology to bring insight to the body of scientific knowledge.”

The Preimplantation period involves the first cellular differentiation events in mammalian development including the formation of pluripotent cell from where embryonic stem (ES) cells are derived. Being one of the simplest mammalian developmental systems to study, it can provide comprehensive understanding of the complex molecular control of reprogramming and cell fate decisions.

Scientists at the Genome Institute of Singapore (GIS) have recently generated significant single cell expression data crucial for a detailed molecular understanding of mammalian development from fertilization to embryo implantation, a process known as the preimplantation period. The knowledge gained has a direct impact on clinical applications in the areas of regenerative medicine and assisted reproduction. This study, published in Developmental Cell on April 20, 2010, is the first of its kind to apply single cell gene expression analysis of many genes to hundreds of cells in a developmental system. Using the new BioMark microfluidic technology and the mouse preimplantation embryo as a model, the scientists were able to study the expression of 48 genes from individual cells and applied this to analyze over 600 individual cells from the 1-cell to the 64-cell stage of preimplantation development. This high throughput single cell research methodology provides the scientists with the ability to detect dynamic patterns in cellular behaviour, which is unprecedented in the field. Significantly, the findings of the study resolves some of the arguments pertaining to cellular differentiation events and places fibroblast growth factor signalling as the primary event in the later cell fate decisions. Executive Director at the GIS, a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), Professor Edison Liu said, “This remarkable work by Guoji Guo, Mikael Huss, Paul Robson and colleagues uses new microgenomic technologies to map, over time, how a single cell decides to permanently become different parts of an embryo.  Within one division, cells commit to specific developmental lineages by expressing defined sets of genes.  This research now opens the possibility of assessing the genetic triggers for fate determination of individual cells in developmental time. On another level, this work highlights the importance of new microtechnologies in advancing the understanding of early embryonic events. “ Professor Davor Solter, Senior Principal Investigator of the Institute of Medical Biology, A*STAR, added, “This is a real technological tour de force. The authors investigated changes in expression of multiple genes on the single cell level during preimplantation mouse development. They clearly demonstrated gradual and stochastic lineage allocation and absence of predetermination. These results conclusively resolved one of the hotly debated issues in mammalian development and provided important new insight into the mechanism which regulates early development in mammals.” "These are important findings.  The team at GIS provided a new look into the complex and little-understood process of early embryo development.  It also demonstrates the power of single cell gene expression.  It is clear that individual cells and small groups of cells behave differently than the aggregate population, and these differences are key to understanding the biology of the system as a whole." said Gajus Worthington,  president and chief executive officer of Fluidigm.  "It always provides a special thrill when researchers use the capabilities of Fluidigm's technology to bring insight to the body of scientific knowledge." The Preimplantation period involves the first cellular differentiation events in mammalian development including the formation of pluripotent cell from where embryonic stem (ES) cells are derived. Being one of the simplest mammalian developmental systems to study, it can provide comprehensive understanding of the complex molecular control of reprogramming and cell fate decisions.

100-fold increase in efficiency in reprogramming human cells to induced stem cells

Researchers from the Wellcome Trust Sanger Institute have today (07/10/2011) announced a new technique to reprogramme human cells, such as skin cells, into stem cells. Their process increases the efficiency of cell reprogramming by one hundred-fold and generates cells of a higher quality at a faster rate.

Until now cells have been reprogrammed using four specific regulatory proteins. By adding two further regulatory factors, Liu and co-workers brought about a dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development. The new streamlined process produces cells that can grow more easily.

“This research is a milestone in human stem cells,” explains Wei Wang, first author on the research from the Wellcome Trust Sanger Institute. “Our technique provides a foundation to unlock the full potential of stem cells.”

Stem cells are unspecialized cells that are able to renew themselves through cell division and can be induced to become functional tissue- or organ-specific cells. It is hoped that stem cells will be used to replace dying or damaged cells with healthy, functional cells. This could have wide-ranging uses in medicine such as organ replacement, bone replacement and treatment of neurodegenerative diseases.

With more than 20 years of research, gold standard stem cells are derived from mice, largely because they are easy to work with and provide accurate and reproducible results. The team’s aim was to develop human cells of equivalent quality to mouse stem cells.

“The reprogrammed cells developed by our team have proved to have the same capabilities as mouse stem cells,” states Pentao Liu, senior author from the Sanger Institute. “Our approach will enable researchers to easily engineer and reprogramme human stem cells to generate cell types for cell replacement therapies in humans.”

Retinoic acid receptor gamma (RAR-γ) and liver receptor homolog (Lrh-1), the additional regulatory factors used by Liu and co-workers, were introduced into the skin cells along with the four other regulatory proteins. The team’s technology produced reprogrammed cells after just four days, compared to the seven days required for the four-protein approach. Key indicators of successfully reprogrammed cells, Oct4 and Rex-1 genes, were seen to be switched on much faster in a much higher number of cells, demonstrating increased efficiency in reprogramming.

“This is the most promising and exciting development in our attempt to develop human stem cells that lend themselves in practical applications. It bears comparison to other technologies as it is simple, robust and reliable,” says Allan Bradley, Senior Group Leader and Director of Emeritus at Sanger Institute.

Contact: Don Powell
press.office@sanger.ac.uk
+44-122-349-6928

Trust Sanger Institute

100-fold increase in efficiency in reprogramming human cells to induced stem cells Researchers from the Wellcome Trust Sanger Institute have today (07/10/2011) announced a new technique to reprogramme human cells, such as skin cells, into stem cells. Their process increases the efficiency of cell reprogramming by one hundred-fold and generates cells of a higher quality at a faster rate. Until now cells have been reprogrammed using four specific regulatory proteins. By adding two further regulatory factors, Liu and co-workers brought about a dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development. The new streamlined process produces cells that can grow more easily. "This research is a milestone in human stem cells," explains Wei Wang, first author on the research from the Wellcome Trust Sanger Institute. "Our technique provides a foundation to unlock the full potential of stem cells." Stem cells are unspecialized cells that are able to renew themselves through cell division and can be induced to become functional tissue- or organ-specific cells. It is hoped that stem cells will be used to replace dying or damaged cells with healthy, functional cells. This could have wide-ranging uses in medicine such as organ replacement, bone replacement and treatment of neurodegenerative diseases. With more than 20 years of research, gold standard stem cells are derived from mice, largely because they are easy to work with and provide accurate and reproducible results. The team's aim was to develop human cells of equivalent quality to mouse stem cells. "The reprogrammed cells developed by our team have proved to have the same capabilities as mouse stem cells," states Pentao Liu, senior author from the Sanger Institute. "Our approach will enable researchers to easily engineer and reprogramme human stem cells to generate cell types for cell replacement therapies in humans." Retinoic acid receptor gamma (RAR-γ) and liver receptor homolog (Lrh-1), the additional regulatory factors used by Liu and co-workers, were introduced into the skin cells along with the four other regulatory proteins. The team's technology produced reprogrammed cells after just four days, compared to the seven days required for the four-protein approach. Key indicators of successfully reprogrammed cells, Oct4 and Rex-1 genes, were seen to be switched on much faster in a much higher number of cells, demonstrating increased efficiency in reprogramming. "This is the most promising and exciting development in our attempt to develop human stem cells that lend themselves in practical applications. It bears comparison to other technologies as it is simple, robust and reliable," says Allan Bradley, Senior Group Leader and Director of Emeritus at Sanger Institute.   Contact: Don Powell press.office@sanger.ac.uk +44-122-349-6928 Trust Sanger Institute

New York, NY - A new study by researchers at NYU Langone Medical Center has shown that Wnt signalling, already known to control many biological processes, between hair follicles and melanocyte stem cells can dictate hair pigmentation. The study was published in the June 11, 2011 issue of the journal Cell.

The research was led by Dr. Mayumi Ito, assistant professor in the Ronald O. Pereleman Department of Dermatology at NYU Langone. “We have known for decades that hair follicle stem cells and pigment-producing melanocycte cells collaborate to produce coloured hair, but the underlying reasons were unknown,” said Dr. Ito. “We discovered Wnt signalling is essential for coordinated actions of these two stem cell lineages and critical for hair pigmentation.” The study suggests the manipulation of Wnt signalling may be a novel strategy for targeting pigmentation such as greying hair. The research study also illustrates a model for tissue regeneration.

“The human body has many types of stem cells that have the potential to regenerate other organs,” said Dr. Ito. “The methods behind communication between stem cells of hair and colour during hair replacement may give us important clues to regenerate complex organs containing many different types of cells.”

Using genetic mouse models, researchers were able to examine how Wnt signalling pathways enabled both hair follicle stem cells and melanocyte stem cells to work together to generate hair growth and produce hair colour. Research also showed the depletion (or inhibition or abnormal) Wnt signalling in hair follicle stem cells not only inhibits hair re-growth but also prevents melanocytes stem cell activation required for producing hair colour. The lack of Wnt activation in melanocyte stem cells leads to depigmented or grey hair.

The study raises the possibility that Wnt signalling is a key pathway for the regulation of melanocyte stem cells and shows how melanocyte behaviour is associated with hair regeneration. This insight provides further understanding of diseases in which melanocytes are either appropriately lost such as hair greying or undergo uncontrolled cell growth as in melanoma

New York, NY - A new study by researchers at NYU Langone Medical Center has shown that Wnt signalling, already known to control many biological processes, between hair follicles and melanocyte stem cells can dictate hair pigmentation. The study was published in the June 11, 2011 issue of the journal Cell. The research was led by Dr. Mayumi Ito, assistant professor in the Ronald O. Pereleman Department of Dermatology at NYU Langone. “We have known for decades that hair follicle stem cells and pigment-producing melanocycte cells collaborate to produce coloured hair, but the underlying reasons were unknown,” said Dr. Ito. “We discovered Wnt signalling is essential for coordinated actions of these two stem cell lineages and critical for hair pigmentation.” The study suggests the manipulation of Wnt signalling may be a novel strategy for targeting pigmentation such as greying hair. The research study also illustrates a model for tissue regeneration. “The human body has many types of stem cells that have the potential to regenerate other organs,” said Dr. Ito. “The methods behind communication between stem cells of hair and colour during hair replacement may give us important clues to regenerate complex organs containing many different types of cells.” Using genetic mouse models, researchers were able to examine how Wnt signalling pathways enabled both hair follicle stem cells and melanocyte stem cells to work together to generate hair growth and produce hair colour. Research also showed the depletion (or inhibition or abnormal) Wnt signalling in hair follicle stem cells not only inhibits hair re-growth but also prevents melanocytes stem cell activation required for producing hair colour. The lack of Wnt activation in melanocyte stem cells leads to depigmented or grey hair. The study raises the possibility that Wnt signalling is a key pathway for the regulation of melanocyte stem cells and shows how melanocyte behaviour is associated with hair regeneration. This insight provides further understanding of diseases in which melanocytes are either appropriately lost such as hair greying or undergo uncontrolled cell growth as in melanoma  

A PILL that enables damaged hearts to repair themselves could be a reality within ten years, thanks to a British stem-cell breakthrough.

Scientists have discovered that a natural embryo molecule can awaken dormant repair cells in adult hearts. It could form the basis of a drug that helps destroyed heart muscle to be rebuilt after a heart attack.

Tests on mice showed it was possible to o improve the pumping efficiency of damaged hearts by 25 per cent. Half that level of benefit could transform the lives of millions of people suffering the devastating after-effects of a heart attack.

Professor Peter Weissberg, medical director of the British Heart Foundation, which funded the research led by University College London scientists, said: “Even five years ago, people would have said this is science fiction, science fantasy.”

Until recently, experts agreed that the heart was inherently irreparable. Once it was damaged, it stayed damaged.

Then research on the changes that occur in embryos developing in the womb led to a rethink.

Scientists learned that stem cells which build the heart in the growing embryo are also present in adults, but dormant.

The breakthrough discovery was that a peptide – a protein building block – called thymosin beta 4 (Tbeta4) which is normally active in the embryo could “re-awaken” the adult stem cells.

Scientists found they could “prime” the hearts of healthy mice for repair by injecting them with Tbeta4.

A “booster” dose of the peptide after a subsequent heart attack reactivated the stem cells and marshalled them into action. Not only did they build new heart muscle, but the cells were electrically “bonded” with existing muscle and able to contract in sync with the rest of the organ. The results were published online today in the journal Nature.

Researchers are now looking at ways of “tweaking” the process to make it more efficient – possibly by finding more powerful alternative molecules that have a similar effect as Tbeta4.

At a “conservative” estimate, they believe a practical treatment could be available in ten years.

This might be an injection or even a pill given to people known to be at risk of a heart attack. They could be patients who suffer from angina, individuals with high blood pressure or high cholesterol, or those whose close relatives have had heart trouble.

A PILL that enables damaged hearts to repair themselves could be a reality within ten years, thanks to a British stem-cell breakthrough. Scientists have discovered that a natural embryo molecule can awaken dormant repair cells in adult hearts. It could form the basis of a drug that helps destroyed heart muscle to be rebuilt after a heart attack. Tests on mice showed it was possible to o improve the pumping efficiency of damaged hearts by 25 per cent. Half that level of benefit could transform the lives of millions of people suffering the devastating after-effects of a heart attack. Professor Peter Weissberg, medical director of the British Heart Foundation, which funded the research led by University College London scientists, said: "Even five years ago, people would have said this is science fiction, science fantasy." Until recently, experts agreed that the heart was inherently irreparable. Once it was damaged, it stayed damaged. Then research on the changes that occur in embryos developing in the womb led to a rethink. Scientists learned that stem cells which build the heart in the growing embryo are also present in adults, but dormant. The breakthrough discovery was that a peptide - a protein building block - called thymosin beta 4 (Tbeta4) which is normally active in the embryo could "re-awaken" the adult stem cells. Scientists found they could "prime" the hearts of healthy mice for repair by injecting them with Tbeta4. A "booster" dose of the peptide after a subsequent heart attack reactivated the stem cells and marshalled them into action. Not only did they build new heart muscle, but the cells were electrically "bonded" with existing muscle and able to contract in sync with the rest of the organ. The results were published online today in the journal Nature. Researchers are now looking at ways of "tweaking" the process to make it more efficient - possibly by finding more powerful alternative molecules that have a similar effect as Tbeta4. At a "conservative" estimate, they believe a practical treatment could be available in ten years. This might be an injection or even a pill given to people known to be at risk of a heart attack. They could be patients who suffer from angina, individuals with high blood pressure or high cholesterol, or those whose close relatives have had heart trouble.  

Do not use the word stem, talk about regenerative medicine instead. That’s the advice given to Swedish researchers from Arnd Hoevel the EU Directorate for Research in Brussels.

The term stem cell is too loaded to be used towards the general public. It says Arnd Hoevel, head of the Health and biotechnology at the EU Directorate for Research in Brussels.

- There are a lot of antibodies to the word stem, he says. I think you should instead use the term regenerative medicine against the EU’s population.

Within the EU there are several research programs on stem cells and how they should be used to develop advanced therapies for severe diseases. But to speak plainly to the public is a sensitive chapter, said Arnd Hoevel at the stem cell conference this week was held in Gothenburg.

The background is the moral-ethical debate about stem cells that collapsed during the early 2000s.Then came all the stem cells from a few days old embryos left over from IVF and were discarded. The cells were taken just to be where the parents gave their consent.

The hope was to get the immature cells that develop into the specialized cells needed to cure serious diseases such as Parkinson’s and Alzheimer’s. But having human life as starting material runs counter to include Christian values that all life is sacred, and led to a stormy ethical debate whether it is right to destroy embryos to find cures for the seriously ill.

For two years, there is a new type of stem cells and the embryo appears to have potential to develop into all cell types. They are called iPS cells, and produced by reprogramming skin or blood cells so that they go backwards in their development to eventually become a stem cell.

From there, they can be programmed to become nerve cells, heart muscle cells or another cell type that is needed to repair a damaged organs or cure diseases.Still there are no clinical treatments, but research is intense in Europe as well as outside.

But the EU has the memory and the worry over the charge in the word stem not faded.

- IPS cells can probably be accepted in many countries. But I still think it is better to talk about regenerative medicine instead, says Arnd Hoevel.

Glossary:

Immature stem cell origin of cell that has the ability to develop into many different specialized cells.

Embryonic stem cell. Available in fertilized eggs that are less than one week.The first few days, all stem cells develop into was the new embryo, after a week they have had time to specialize more. Embryonic stem cells taken from embryos five to seven days after fertilization.

IPS cells (induced pluripotent stem cells). Fully developed cells after gene transfer gone backwards in their development and become a stem cell (immature cell origin) again.

Regenerative medicine: A collective name for methods that replace damaged cells or tissues in the body with new cells. Today the focus of much research in the field of stem cells.

Do not use the word stem, talk about regenerative medicine instead. That’s the advice given to Swedish researchers from Arnd Hoevel the EU Directorate for Research in Brussels.   The term stem cell is too loaded to be used towards the general public. It says Arnd Hoevel, head of the Health and biotechnology at the EU Directorate for Research in Brussels. - There are a lot of antibodies to the word stem, he says. I think you should instead use the term regenerative medicine against the EU's population. Within the EU there are several research programs on stem cells and how they should be used to develop advanced therapies for severe diseases. But to speak plainly to the public is a sensitive chapter, said Arnd Hoevel at the stem cell conference this week was held in Gothenburg. The background is the moral-ethical debate about stem cells that collapsed during the early 2000s.Then came all the stem cells from a few days old embryos left over from IVF and were discarded. The cells were taken just to be where the parents gave their consent. The hope was to get the immature cells that develop into the specialized cells needed to cure serious diseases such as Parkinson's and Alzheimer's. But having human life as starting material runs counter to include Christian values that all life is sacred, and led to a stormy ethical debate whether it is right to destroy embryos to find cures for the seriously ill. For two years, there is a new type of stem cells and the embryo appears to have potential to develop into all cell types. They are called iPS cells, and produced by reprogramming skin or blood cells so that they go backwards in their development to eventually become a stem cell. From there, they can be programmed to become nerve cells, heart muscle cells or another cell type that is needed to repair a damaged organs or cure diseases.Still there are no clinical treatments, but research is intense in Europe as well as outside. But the EU has the memory and the worry over the charge in the word stem not faded. - IPS cells can probably be accepted in many countries. But I still think it is better to talk about regenerative medicine instead, says Arnd Hoevel. Glossary: Immature stem cell origin of cell that has the ability to develop into many different specialized cells. Embryonic stem cell. Available in fertilized eggs that are less than one week.The first few days, all stem cells develop into was the new embryo, after a week they have had time to specialize more. Embryonic stem cells taken from embryos five to seven days after fertilization. IPS cells (induced pluripotent stem cells). Fully developed cells after gene transfer gone backwards in their development and become a stem cell (immature cell origin) again. Regenerative medicine: A collective name for methods that replace damaged cells or tissues in the body with new cells. Today the focus of much research in the field of stem cells.    

http://www.guardian.co.uk/world/2011/mar/29/japan-cell-transplants-nuclear-workers

http://www.guardian.co.uk/world/2011/mar/29/japan-cell-transplants-nuclear-workers

http://www.wbir.com/health/article/153097/3/Americans-are-going-abroad-for-stem-cell-treatment

http://www.wbir.com/health/article/153097/3/Americans-are-going-abroad-for-stem-cell-treatment

http://abclocal.go.com/kabc/story?section=news/local/los_angeles&id=7755202

http://abclocal.go.com/kabc/story?section=news/local/los_angeles&id=7755202

http://www.prnewswire.com/news-releases/thermogenesis-signs-major-bone-marrow-product-distribution-agreement-in-china-106714148.html

http://www.prnewswire.com/news-releases/thermogenesis-signs-major-bone-marrow-product-distribution-agreement-in-china-106714148.html

http://www.eurekalert.org/pub_releases/2010-11/si-fsc110210.php

http://www.eurekalert.org/pub_releases/2010-11/si-fsc110210.php