[naturenews] from [nature.com]
[naturenews]
Published online 13 December 2009 | Nature | doi:10.1038/news.2009.1140
News
Stem-cell induction made simpler
Induced pluripotent stem cells made by inserting genes at just one location.
Brendan Borrell
{{Mouse cells can be reprogrammed by a single cassette of genes.}
CORBIS}
Adult mouse cells can now be reprogrammed to a stem-cell-like state with the help of a single genetic insertion — rather than the multiple gene insertions required in the past. The advance also enables reprogrammable mice to be maintained in the lab generation after generation.
Three years ago, Shinya Yamanaka at Kyoto University and his colleagues made a splash by creating the first induced pluripotent stem (iPS) cells, which can develop into any of the body's cell types. Because they are obtained using adult body cells, iPS cells hold the potential for being used to develop human therapies without the ethical concerns associated with stem cells obtained from embryos. So far, iPS cells have been reprogrammed from a wide variety of somatic cell types, including skin, blood and liver cells, but scientists are still unsure how iPS cells compare to true embryonic stem cells.
One challenge has been the fact that to induce pluripotency, four reprogramming genes must be inserted into the genome — Oct4, Sox2, Klf4 and c-Myc. This requires the use of multiple retroviruses, meaning the genes end up in random locations in the mouse genome, which can interfere with the function of the mouse's own genes. Moreover, offspring of these mice must be screened to ensure that they contain all of the required reprogramming genes.
Now, two teams of researchers — one led by Rudolf Jaenisch at the Massachusetts Institute of Technology in Cambridge and the other led by his former student Konrad Hochedlinger at Harvard University, also in Cambridge, Massachusetts — describe a technique in Nature Methods that avoids these difficulties1,2.
Time-saver
The researchers combined the four mouse reprogramming genes onto a piece of DNA, known as a cassette, which they inserted at a single locus in the mouse genome. The mice were then bred, and their somatic cells were transformed into iPS cells following the addition of the antibiotic doxycycline, which triggers the cassette to express the four reprogramming genes.
{{“The problem with a virus is that you never really know where it landed in the genome.”}
Konrad Hochedlinger
Harvard University}
"The advantage of this method is that the single gene has been introduced to a defined locus," says Hochedlinger, "The problem with a virus is that you never really know where it landed in the genome or how well it was expressed." By eliminating this variability, Hochedlinger says that the technique will eliminate the need for further screening in the mice and free up the equivalent of one full-time employee in his lab. "I'm very happy," he says.
The technique may also help to answer lingering doubts about the differences between iPS cells and embryonic stem cells. A study earlier this year in Cell Stem Cell showed that hundreds of genes are differentially expressed in the two cell types3, and another revealed that iPS cells are not as efficient as embryonic stem cells at differentiating into all cell types4. Matthias Stadtfeld of Harvard University, who is first author on one of the reprogramming studies2, says that it will now be possible to compare two genetically matched cell types and ask if iPS cells are as useful as embryonic stem cells. "We are fairly confident you can reprogram any cell type, the question is: are we ending up with the same quality of cells in the end?"
Super strains
Other experts agree that the advance will circumvent limitations with iPS technologies. "I've been hoping these guys would make these strains of mice," says stem-cell biologist George Daley of the Children's Hospital in Boston, Massachusetts, who was not involved in the research.
Although some researchers have developed non-genetic systems to reprogram cells using proteins or small molecules (see 'Stem-cell therapies closer to the clinic'), Daley points out that such methods are currently "incredibly inefficient". To improve efficiency and safety so that these techniques can be used in humans, scientists could potentially create lines of mice with just three of the four reprogramming genes, and screen for chemicals that could be used as an alternative to inserting the fourth reprogramming gene.
"Fundamentally, everyone is looking to improve the efficiency of reprogramming using chemicals, proteins and the like," Daley says. "These two papers give you a substrate on which to work."
References
1. Carey, B. W., Markoulaki, S., Beard, C., Hanna, J. & Jaenisch, R. Nature Methods advance online publication doi:10.1038/nmeth.1410 (2009).
2. Stadtfeld, M., Maherali, N., Borkent, M. & Hochedlinger, K. Nature Methods advance online publication doi:10.1038/nmeth.1409 (2009).3. Chin, M. H. et al. Cell Stem Cell 5, 111-123 (2009).
4. Zhao, X.-Y. et al. Nature 461, 86-90 (2009).
[naturenews]
Published online 13 December 2009 | Nature | doi:10.1038/news.2009.1141
News
Genome reveals panda's carnivorous side
Bamboo-eater seemingly has no genes for cellulose-digesting enzymes.
Jane Qiu
{{Jingjing, the three-year-old female panda whose genome has been sequenced.}
Zhihe Zhang}
The complete genetic sequence of the giant panda has revealed that the iconic Chinese bear has all the genes required to digest meat — but not its staple food, bamboo.
The international team sequenced a three-year-old female panda called Jingjing, who was also a mascot of the 2008 Beijing Olympics, and found that she lacks any recognizable genes for cellulases — enzymes that break down the plant material cellulose. "The panda's bamboo diet may be dictated by its gut bacteria rather than by its own genetic composition," says Wang Jun, deputy director of the Beijing Genomics Institute in Shenzhen, Guangdong province, who led the sequencing project.
The researchers also discovered that the T1R1 gene, which encodes a key receptor for the savoury or 'umami' flavour of meat, has become an inactive 'pseudogene' due to two mutations. "This may explain why the panda diet is primarily herbivorous even though it is classified as a carnivore," says Wang.
The research, published in Nature1, shows that pandas have about 21,000 genes packed into 21 pairs of chromosomes, including one pair of sex chromosomes. Of all the mammals that have been sequenced, pandas are most similar to dogs — with 80% similarity — and are only 68% similar to humans.
But the bear's genome has undergone fewer genetic changes over time than those of dogs and humans, suggesting that it evolved more slowly. The panda is often regarded as a 'living fossil' because its ancestors are thought to have lived in China more than eight million years ago.
The study also shows pandas have a high degree of genetic diversity — about twice as much as humans. "This shows that the panda has a good chance of survival despite its small population size," says Wang.
"The study has laid the biological foundation to better understand pandas, and has the potential for improving conservation by controlling diseases and boosting reproduction of the species," says Jianguo Liu, a conservation biologist at Michigan State University in East Lansing, Missouri, who was not involved in the study.
Habitat threat
But critics stress that protecting the panda's increasingly fragmented and shrinking habitat is a more pressing issue in their conservation. China is thought to be home to around 1,600 wild pandas — though the actual number is hotly debated. Another 300 or so live in captivity.
Some conservationists, such as Fan Zhiyong, director of the conservation group WWF's China species programme, believe that the panda genome will have little impact on conservation efforts. "Protecting pandas in the wild remains the top priority, but their habitats are becoming smaller and smaller," says Fan. "If we don't have any wild pandas one day, what can we do with their genes?"
Although China has set up several panda sanctuaries since the 1960s, economic development often takes precedence over conservation. Consequently, pandas' habitats are often invaded by construction projects such as dams and highways. Tourism is also a big threat because pandas are reclusive creatures. For example, Jiuzhaigou, a panda sanctuary in Sichuan, is visited by millions of tourists every year. "You don't see any pandas there anymore," says Fan. "This is hardly surprising."
There is "no doubt" that information from the genome and habitat protection are both crucial for conservation efforts, says Wang. The panda genome, the first in a string of sequencing efforts by the Shenzhen institute, will be a test of how such genetic information can help in the conservation of endangered species, he adds. The team has got a draft genome map of the polar bear, and has started sequencing the genome of the Tibetan antelope.
References
1. Li, R. et al. Nature doi:10.1038/nature08696 (2009).
[naturenews]
Published online 13 December 2009 | Nature | doi:10.1038/news.2009.1140
News
Stem-cell induction made simpler
Induced pluripotent stem cells made by inserting genes at just one location.
Brendan Borrell
{{Mouse cells can be reprogrammed by a single cassette of genes.}
CORBIS}
Adult mouse cells can now be reprogrammed to a stem-cell-like state with the help of a single genetic insertion — rather than the multiple gene insertions required in the past. The advance also enables reprogrammable mice to be maintained in the lab generation after generation.
Three years ago, Shinya Yamanaka at Kyoto University and his colleagues made a splash by creating the first induced pluripotent stem (iPS) cells, which can develop into any of the body's cell types. Because they are obtained using adult body cells, iPS cells hold the potential for being used to develop human therapies without the ethical concerns associated with stem cells obtained from embryos. So far, iPS cells have been reprogrammed from a wide variety of somatic cell types, including skin, blood and liver cells, but scientists are still unsure how iPS cells compare to true embryonic stem cells.
One challenge has been the fact that to induce pluripotency, four reprogramming genes must be inserted into the genome — Oct4, Sox2, Klf4 and c-Myc. This requires the use of multiple retroviruses, meaning the genes end up in random locations in the mouse genome, which can interfere with the function of the mouse's own genes. Moreover, offspring of these mice must be screened to ensure that they contain all of the required reprogramming genes.
Now, two teams of researchers — one led by Rudolf Jaenisch at the Massachusetts Institute of Technology in Cambridge and the other led by his former student Konrad Hochedlinger at Harvard University, also in Cambridge, Massachusetts — describe a technique in Nature Methods that avoids these difficulties1,2.
Time-saver
The researchers combined the four mouse reprogramming genes onto a piece of DNA, known as a cassette, which they inserted at a single locus in the mouse genome. The mice were then bred, and their somatic cells were transformed into iPS cells following the addition of the antibiotic doxycycline, which triggers the cassette to express the four reprogramming genes.
{{“The problem with a virus is that you never really know where it landed in the genome.”}
Konrad Hochedlinger
Harvard University}
"The advantage of this method is that the single gene has been introduced to a defined locus," says Hochedlinger, "The problem with a virus is that you never really know where it landed in the genome or how well it was expressed." By eliminating this variability, Hochedlinger says that the technique will eliminate the need for further screening in the mice and free up the equivalent of one full-time employee in his lab. "I'm very happy," he says.
The technique may also help to answer lingering doubts about the differences between iPS cells and embryonic stem cells. A study earlier this year in Cell Stem Cell showed that hundreds of genes are differentially expressed in the two cell types3, and another revealed that iPS cells are not as efficient as embryonic stem cells at differentiating into all cell types4. Matthias Stadtfeld of Harvard University, who is first author on one of the reprogramming studies2, says that it will now be possible to compare two genetically matched cell types and ask if iPS cells are as useful as embryonic stem cells. "We are fairly confident you can reprogram any cell type, the question is: are we ending up with the same quality of cells in the end?"
Super strains
Other experts agree that the advance will circumvent limitations with iPS technologies. "I've been hoping these guys would make these strains of mice," says stem-cell biologist George Daley of the Children's Hospital in Boston, Massachusetts, who was not involved in the research.
Although some researchers have developed non-genetic systems to reprogram cells using proteins or small molecules (see 'Stem-cell therapies closer to the clinic'), Daley points out that such methods are currently "incredibly inefficient". To improve efficiency and safety so that these techniques can be used in humans, scientists could potentially create lines of mice with just three of the four reprogramming genes, and screen for chemicals that could be used as an alternative to inserting the fourth reprogramming gene.
"Fundamentally, everyone is looking to improve the efficiency of reprogramming using chemicals, proteins and the like," Daley says. "These two papers give you a substrate on which to work."
References
1. Carey, B. W., Markoulaki, S., Beard, C., Hanna, J. & Jaenisch, R. Nature Methods advance online publication doi:10.1038/nmeth.1410 (2009).
2. Stadtfeld, M., Maherali, N., Borkent, M. & Hochedlinger, K. Nature Methods advance online publication doi:10.1038/nmeth.1409 (2009).3. Chin, M. H. et al. Cell Stem Cell 5, 111-123 (2009).
4. Zhao, X.-Y. et al. Nature 461, 86-90 (2009).
[naturenews]
Published online 13 December 2009 | Nature | doi:10.1038/news.2009.1141
News
Genome reveals panda's carnivorous side
Bamboo-eater seemingly has no genes for cellulose-digesting enzymes.
Jane Qiu
{{Jingjing, the three-year-old female panda whose genome has been sequenced.}
Zhihe Zhang}
The complete genetic sequence of the giant panda has revealed that the iconic Chinese bear has all the genes required to digest meat — but not its staple food, bamboo.
The international team sequenced a three-year-old female panda called Jingjing, who was also a mascot of the 2008 Beijing Olympics, and found that she lacks any recognizable genes for cellulases — enzymes that break down the plant material cellulose. "The panda's bamboo diet may be dictated by its gut bacteria rather than by its own genetic composition," says Wang Jun, deputy director of the Beijing Genomics Institute in Shenzhen, Guangdong province, who led the sequencing project.
The researchers also discovered that the T1R1 gene, which encodes a key receptor for the savoury or 'umami' flavour of meat, has become an inactive 'pseudogene' due to two mutations. "This may explain why the panda diet is primarily herbivorous even though it is classified as a carnivore," says Wang.
The research, published in Nature1, shows that pandas have about 21,000 genes packed into 21 pairs of chromosomes, including one pair of sex chromosomes. Of all the mammals that have been sequenced, pandas are most similar to dogs — with 80% similarity — and are only 68% similar to humans.
But the bear's genome has undergone fewer genetic changes over time than those of dogs and humans, suggesting that it evolved more slowly. The panda is often regarded as a 'living fossil' because its ancestors are thought to have lived in China more than eight million years ago.
The study also shows pandas have a high degree of genetic diversity — about twice as much as humans. "This shows that the panda has a good chance of survival despite its small population size," says Wang.
"The study has laid the biological foundation to better understand pandas, and has the potential for improving conservation by controlling diseases and boosting reproduction of the species," says Jianguo Liu, a conservation biologist at Michigan State University in East Lansing, Missouri, who was not involved in the study.
Habitat threat
But critics stress that protecting the panda's increasingly fragmented and shrinking habitat is a more pressing issue in their conservation. China is thought to be home to around 1,600 wild pandas — though the actual number is hotly debated. Another 300 or so live in captivity.
Some conservationists, such as Fan Zhiyong, director of the conservation group WWF's China species programme, believe that the panda genome will have little impact on conservation efforts. "Protecting pandas in the wild remains the top priority, but their habitats are becoming smaller and smaller," says Fan. "If we don't have any wild pandas one day, what can we do with their genes?"
Although China has set up several panda sanctuaries since the 1960s, economic development often takes precedence over conservation. Consequently, pandas' habitats are often invaded by construction projects such as dams and highways. Tourism is also a big threat because pandas are reclusive creatures. For example, Jiuzhaigou, a panda sanctuary in Sichuan, is visited by millions of tourists every year. "You don't see any pandas there anymore," says Fan. "This is hardly surprising."
There is "no doubt" that information from the genome and habitat protection are both crucial for conservation efforts, says Wang. The panda genome, the first in a string of sequencing efforts by the Shenzhen institute, will be a test of how such genetic information can help in the conservation of endangered species, he adds. The team has got a draft genome map of the polar bear, and has started sequencing the genome of the Tibetan antelope.
References
1. Li, R. et al. Nature doi:10.1038/nature08696 (2009).
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