Category Archives: Stem Cells

Public release date: 2-Mar-2012 [ | E-mail | Share ]

Contact: Klaus Hansen klaus.hansen@bric.ku.dk (45) 21-15-55-64 University of Copenhagen

Upon fertilisation, a single cell is formed when egg and sperm fuse. Our entire body, with more than 200 specialised cell types and billions of cells are formed from this single cell. It is a scientific mystery how the early stem cells know what cell type to become, but a precise timing of the process is crucial for correct development and function of our body. Researchers across the world chase knowledge about our stem cells, as this knowledge holds great promises for development of treatment against several major diseases. Researchers from BRIC, University of Copenhagen, have just shown that the molecule REST acts as an adapter in stem cells, coupling molecular on-off switches with neural genes and thereby times neuronal development.

"REST secure neuronal genes to be turned off in our stem cells until the correct time point in fetal life, where the molecule is lost and development of the nervous system begins. Our results are very important for the understanding of how genes are turned on and off during fetal development, but also relates to disease development such as cancer. Hopefully, our future studies of REST will contribute to the development of new types of treatments," says Associate Professor and Group Leader at BRIC, Klaus Hansen.

Genetic switches

All our cells contain the same DNA, yet they can develop into specialised cells with different shapes and functions. This ability is due to only selective genes being turned on in for example neuronal cells and other genes in liver cells and skin cells. Postdoc Nikolaj Dietrich from Klaus Hansen's laboratory has been the main driver of the investigation:

"Our results show that REST act as an adapter for the protein complexes called PRCs, connecting these complexes to neuronal genes. The PRCs are genetic switches turning off genes and therefore REST and the PRCs act in concert to shutdown neuronal genes. A similar mechanism has previously been described in fruit flies, but until now, no one has been able to identify such adapter-molecules in humans or other mammals. This has led to various biological hypotheses, but now we are able to show that this genetic mechanism has been conserved trough out evolution," says Nikolaj Dietrich.

Brain damage and brain tumors

REST and PRC are attached to neuronal genes in the early fetal stem cells, keeping neuronal genes turned off. During fetal development, REST disappears in cells that are determined to develop into neuronal cells, whereas the molecule is preserved in other cell types. REST is also preserved in special neuronal stem cells, ensuring that these cells maintain their stem cell properties. This is crucial if we experience damage to our nervous system later in life, as only the neuronal stem cells can repair the damage by giving rise to new neurons and thereby secure vital body functions. However, REST also appears to be associated with a higher risk of cancer:

"An increased amount of REST has been found in the brain tumor form called neuroblastoma. Some of our results indicate that REST may be involved in cancer, as the molecule can turn off some growth-inhibitory and cancer-protective genes called tumor suppressors. This possible action of REST is the focus of ongoing studies," says Nikolaj Dietrich.

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'REST' is crucial for the timing of brain development

Public release date: 1-Mar-2012 [ | E-mail | Share ]

Contact: Stephen Dalton sdalton@uga.edu 706-542-9857 University of Georgia

Athens, Ga. Despite the promise associated with the therapeutic use of human stem cells, a complete understanding of the mechanisms that control the fundamental question of whether a stem cell becomes a specific cell type within the body or remains a stem cell hasuntil noweluded scientists.

A University of Georgia study published in the March 2 edition of the journal Cell Stem Cell, however, creates the first ever blueprint of how stem cells are wired to respond to the external signaling molecules to which they are constantly exposed. The finding, which reconciles years of conflicting results from labs across the world, gives scientists the ability to precisely control the development, or differentiation, of stem cells into specific cell types.

"We can use the information from this study as an instruction book to control the behavior of stem cells," said lead author Stephen Dalton, Georgia Research Alliance Eminent Scholar of Molecular Biology and professor of cellular biology in the UGA Franklin College of Arts and Sciences. "We'll be able to allow them to differentiate into therapeutic cell types much more efficiently and in a far more controlled manner."

The previous paradigm held that individual signaling molecules acted alone to set off a linear chain of events that control the fate of cells. Dalton's study, on the other hand, reveals that a complex interplay of several molecules controls the "switch" that determines whether a stem cell stays in its undifferentiated state or goes on to become a specific cell type, such as a heart, brain or pancreatic cell.

"This work addresses one of the biggest challenges in stem cell researchfiguring out how to direct a stem cell toward becoming a specific cell type," said Marion Zatz, who oversees stem cell biology grants at the National Institutes of Health's National Institute of General Medical Sciences, which partially supported the work.

"In this paper, Dr. Dalton puts together several pieces of the puzzle and offers a model for understanding how multiple signaling pathways coordinate to steer a stem cell toward differentiating into a particular type of cell. This framework ultimately should not only advance a fundamental understanding of embryonic development, but facilitate the use of stem cells in regenerative medicine."

To get a sense of how murky the understanding of stem cell differentiation was, consider that previous studies reached opposite conclusions about the role of a common signaling molecule known as Wnt. About half the published studies found that Wnt kept a molecular switch in an "off" position, which kept the stem cell in its undifferentiated, or pluripotent, state. The other half reached the opposite conclusion.

Could the same Wnt molecule be responsible for both outcomes? As it turns out, the answer is yes. Dalton's team found that in small amounts, Wnt signaling keeps the stem cell in its pluripotent state. In larger quantities, it does the opposite and encourages the cell to differentiate.

Go here to see the original:
UGA study reveals basic molecular 'wiring' of stem cells

A University of Georgia study published in the March 2 edition of the journal Cell Stem Cell, however, creates the first ever blueprint of how stem cells are wired to respond to the external signaling molecules to which they are constantly exposed. The finding, which reconciles years of conflicting results from labs across the world, gives scientists the ability to precisely control the development, or differentiation, of stem cells into specific cell types.

"We can use the information from this study as an instruction book to control the behavior of stem cells," said lead author Stephen Dalton, Georgia Research Alliance Eminent Scholar of Molecular Biology and professor of cellular biology in the UGA Franklin College of Arts and Sciences. "We'll be able to allow them to differentiate into therapeutic cell types much more efficiently and in a far more controlled manner."

The previous paradigm held that individual signaling molecules acted alone to set off a linear chain of events that control the fate of cells. Dalton's study, on the other hand, reveals that a complex interplay of several molecules controls the "switch" that determines whether a stem cell stays in its undifferentiated state or goes on to become a specific cell type, such as a heart, brain or pancreatic cell.

"This work addresses one of the biggest challenges in stem cell researchfiguring out how to direct a stem cell toward becoming a specific cell type," said Marion Zatz, who oversees stem cell biology grants at the National Institutes of Health's National Institute of General Medical Sciences, which partially supported the work.

"In this paper, Dr. Dalton puts together several pieces of the puzzle and offers a model for understanding how multiple signaling pathways coordinate to steer a stem cell toward differentiating into a particular type of cell. This framework ultimately should not only advance a fundamental understanding of embryonic development, but facilitate the use of stem cells in regenerative medicine."

To get a sense of how murky the understanding of stem cell differentiation was, consider that previous studies reached opposite conclusions about the role of a common signaling molecule known as Wnt. About half the published studies found that Wnt kept a molecular switch in an "off" position, which kept the stem cell in its undifferentiated, or pluripotent, state. The other half reached the opposite conclusion.

Could the same Wnt molecule be responsible for both outcomes? As it turns out, the answer is yes. Dalton's team found that in small amounts, Wnt signaling keeps the stem cell in its pluripotent state. In larger quantities, it does the opposite and encourages the cell to differentiate.

But Wnt doesn't work alone. Other molecules, such as insulin-like growth factor (Igf), fibroblast growth factor (Fgf2) and Activin A also play a role. To complicate things further, these signaling molecules amplify each other so that a two-fold increase in one can result in a 10-fold increase in another. The timing with which the signals are introduced matters, too.

"One of the things that surprised us was how all of the pathways 'talk' to each other," Dalton said. "You can't do anything to the Igf pathway without affecting the Fgf2 pathway, and you can't do anything to Fgf2 without affecting Wnt. It's like a house of cards; everything is totally interconnected."

Dalton and his team spent a painstaking five years creating hypotheses about the how the signaling molecules function, testing those hypotheses, andwhen faced with an unexpected resultrebuilding their hypotheses and re-testing. This process continued until the entire system was resolved.

Go here to see the original:
New study reveals basic molecular 'wiring' of stem cells

ScienceDaily (Mar. 1, 2012) Despite the promise associated with the therapeutic use of human stem cells, a complete understanding of the mechanisms that control the fundamental question of whether a stem cell becomes a specific cell type within the body or remains a stem cell has-until now-eluded scientists.

A University of Georgia study published in the March 2 edition of the journal Cell Stem Cell, however, creates the first ever blueprint of how stem cells are wired to respond to the external signaling molecules to which they are constantly exposed. The finding, which reconciles years of conflicting results from labs across the world, gives scientists the ability to precisely control the development, or differentiation, of stem cells into specific cell types.

"We can use the information from this study as an instruction book to control the behavior of stem cells," said lead author Stephen Dalton, Georgia Research Alliance Eminent Scholar of Molecular Biology and professor of cellular biology in the UGA Franklin College of Arts and Sciences. "We'll be able to allow them to differentiate into therapeutic cell types much more efficiently and in a far more controlled manner."

The previous paradigm held that individual signaling molecules acted alone to set off a linear chain of events that control the fate of cells. Dalton's study, on the other hand, reveals that a complex interplay of several molecules controls the "switch" that determines whether a stem cell stays in its undifferentiated state or goes on to become a specific cell type, such as a heart, brain or pancreatic cell.

"This work addresses one of the biggest challenges in stem cell research-figuring out how to direct a stem cell toward becoming a specific cell type," said Marion Zatz, who oversees stem cell biology grants at the National Institutes of Health's National Institute of General Medical Sciences, which partially supported the work.

"In this paper, Dr. Dalton puts together several pieces of the puzzle and offers a model for understanding how multiple signaling pathways coordinate to steer a stem cell toward differentiating into a particular type of cell. This framework ultimately should not only advance a fundamental understanding of embryonic development, but facilitate the use of stem cells in regenerative medicine."

To get a sense of how murky the understanding of stem cell differentiation was, consider that previous studies reached opposite conclusions about the role of a common signaling molecule known as Wnt. About half the published studies found that Wnt kept a molecular switch in an "off" position, which kept the stem cell in its undifferentiated, or pluripotent, state. The other half reached the opposite conclusion.

Could the same Wnt molecule be responsible for both outcomes? As it turns out, the answer is yes. Dalton's team found that in small amounts, Wnt signaling keeps the stem cell in its pluripotent state. In larger quantities, it does the opposite and encourages the cell to differentiate.

But Wnt doesn't work alone. Other molecules, such as insulin-like growth factor (Igf), fibroblast growth factor (Fgf2) and Activin A also play a role. To complicate things further, these signaling molecules amplify each other so that a two-fold increase in one can result in a 10-fold increase in another. The timing with which the signals are introduced matters, too.

"One of the things that surprised us was how all of the pathways 'talk' to each other," Dalton said. "You can't do anything to the Igf pathway without affecting the Fgf2 pathway, and you can't do anything to Fgf2 without affecting Wnt. It's like a house of cards; everything is totally interconnected."

Read more here:
Basic molecular 'wiring' of stem cells revealed

London, Feb 29 (IANS) Children shot with their own stem cells, for the very first time in a rare immune disorder, have shown improvement.

The condition, known as X-CGD, is caused by faulty genes. Doctors were able to take a sample of the children's stem cells, manipulate them in the lab and reintroduce them. This gave the children a working copy of the faulty gene and their condition improved, enabling them to temporarily fight off infections.

It is the third immune disorder that doctors at Great Ormond Street Hospital have successfully tackled. The others were the life-threatening conditions, X-SCID and ada-SCID, and 90 percent of treated children have improved, with some showing signs that their immune system has been normalised for good.

Remy Helbawi, 16, from South London, was the first child with X-CGD to be treated. The condition only affects boys and means that while his body produces the white blood cells to fight viruses it does not have the correct cells to fight off bacterial or fungal infections, The Telegraph reports.

The resulting infections can be life-threatening. Up until now the only treatment has been a bone marrow transplant which would offer a permanent cure.

Remy's brother who also had the disease was found a bone marrow match and was successfully treated that way but no match has been found for Remy and a serious lung infection was threatening his life.

Remy said: "Until I was 10 I had the same life as anyone else, except I had eczema a lot of the time. I didn't have a fungal infection until about ten, but when I got my first fungal infection my life changed. I missed a lot of school, I had lots of tests and was in hospital. I would get exhausted after climbing stairs."

Before undergoing the gene therapy, Remy had to have chemotherapy which made his hair fall out and he was kept in isolation for a month.

Remy's nurse Helen Braggins said: "Remy had been unwell for last two years and began to miss school. He had significant fungal lung disease in January of last year, which was getting worse. Without some radical treatment intervention, Remy would not have survived and was becoming increasingly short of breath."

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Children improve in rare disorder with own stem cells