(Press-News.org) Ever since researchers devised a recipe for turning adult cells into cells that look and act like embryonic stem cells, there has been lingering doubt in the field about just how close to embryonic stem cells each of those cell lines really is at a molecular and functional level. Now, researchers reporting in the February 4th issue of the journal Cell, a Cell Press publication, have developed a systematic way to lay those doubts about quality to rest.
They have devised a method to quickly and comprehensively characterize those cells using a series of genomic assays, ultimately assigning a scorecard to each. The effort has also yielded genome-wide reference maps detailing the epigenetic and gene expression landscapes for several of the so-called induced pluripotent stem cells (iPS) and embryonic stem cell lines that can now be used for comparison by anyone studying an iPS or embryonic cell line. (Epigenetics refers to chemical modifications to DNA that can alter the expression of genes without changing the underlying sequence.)
The advance is critical for the future use of iPS cells in the study of disease, for cell-based drug screening and as a renewable source of cells for transplantation medicine, the researchers say. Overall, the news is quite positive.
"The exciting thing is that this tells us something fundamental about what these cells are," said Kevin Eggan of Harvard University and the Howard Hughes Medical Institute. "It appears that the version 1.0 reprogramming technology is actually pretty good."
In a careful comparison of 20 previously derived human embryonic stem cell lines and 12 human iPS cell lines, the new method does turn up some variation. But the variation observed for many iPS cell lines falls within that seen for embryonic stem cells as well. It appears that the quality of many of those iPS cell lines is high, depending in part on what they might be used for.
"There are different grades of quality," said Alexander Meissner of the Broad Institute and Harvard University. "A particular line might be bad for one purpose but great for an alternative one. This gives us a more refined view."
"Beauty will be in the eye of the beholder," Eggan added. Certain lines might be really good at making one type of tissue, but not as good for making another. Now researchers will have a more accessible way to make that determination reliably without having to rely on guesswork.
Eggan and Meissner report that they were able to assess the similarities and differences among lines and to use those assessments to determine which lines should be avoided for a particular purpose. They were also able to predict the efficiency with which a given iPS cell line used in an independent study would differentiate into motor neurons.
There are methods for assessing iPS cell quality today, but those are rather time consuming and would not be suitable as iPS cell technology is scaled up for broader use. The gold standard assay today involves injecting cells into an immune compromised mouse and allowing those cells to grow and divide for one to three months to see whether they successfully differentiate into all the cell types. "It takes months and it's fairly subjective," Meissner said.
The new method takes just one or two weeks to complete and is much more quantitative. It's possible the assays could be made to go even faster, the researchers said, particularly if industry were to devise a user-friendly kit. Ultimately, this series of assays or other methods along the same lines might be used clinically.
In addition to its practical use for selecting the best cells for a particular task, the findings and scoring method will also offer new insights into the cells themselves, the researchers said.
"We can begin to get to the bottom of the differences among cell lines and their root causes," Eggan said.
###
Publishing in Cell Issue - February 4th, 2011
Bock et al.: "Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines"
For stem cells, a way to keep score
2011-02-04
ELSE PRESS RELEASES FROM THIS DATE:
Ongoing policy uncertainty is detrimental for stem cell scientists
2011-02-04
While there is no doubt that the ethical controversy surrounding human embryonic stem cell (hESC) research has given rise to an uncertain policy environment, the true impact of years of frequent policy changes has not been fully assessed. Now, an article published by Cell Press on February 3rd in the journal Cell Stem Cell reports on a recent survey of several hundred stem cell scientists in the United States and begins to reveal the substantial negative impact that this uncertainty has had on them, including both those who work directly with hESCs and those who work with ...
Destined for disease: Breast cancer mutation regulates cell fate
2011-02-04
A new study sheds light on why individuals who inherit a particular family of mutations have a high risk of developing a very aggressive form of breast cancer. The research, published by Cell Press on February 4th in the journal Cell Stem Cell, shows that breast tissue cells from these individuals make abnormal cell-fate decisions even before cancer develops and provides exciting new insights into the mechanisms behind one of the most lethal types of breast cancer.
There are many forms of human breast cancer. Mutations in the BRCA1 tumor suppressor gene are associated ...
Northern Mars landscape actively changing
2011-02-04
Sand dunes in a vast area of northern Mars long thought to be frozen in time are changing with both sudden and gradual motions, as revealed by images from a high-resolution camera aboard NASA's Mars Reconnaissance Orbiter, or MRO.
These dune fields cover an area the size of Texas in a band around the planet at the edge of Mars' north polar cap. Although the new findings suggest they are among the most active landscapes on Mars, few changes in these dark-toned dunes had been detected before a campaign of repeated imaging by the High Resolution Imaging Science Experiment ...
Plant's immune defense revs up for the morning attack
2011-02-04
DURHAM, N.C. – Timing is everything in the long-standing arms race between the flowering plant Arabidopsis and Hyaloperonospora, a downy mildew pathogen.
Duke University researchers have found that the little mustard plant cranks up its immune system in the morning to prepare for the greatest onslaught of infectious spores released by the mildew.
It isn't news that plants know what time of day it is and change their activities accordingly, but this is the first time that a plant's defensive systems have been shown to cycle on a daily basis – even when pathogens aren't ...
Animal with the most genes? A tiny crustacean
2011-02-04
BLOOMINGTON, Ind. -- Complexity ever in the eye of its beholders, the animal with the most genes -- about 31,000 -- is the near-microscopic freshwater crustacean Daphnia pulex, or water flea. By comparison, humans have about 23,000 genes. Daphnia is the first crustacean to have its genome sequenced.
The findings are part of a comprehensive report in this week's Science by members of the Daphnia Genomics Consortium, an international network of scientists led by the Center for Genomics and Bioinformatics (CGB) at Indiana University Bloomington and the U.S. Department of ...
Quantum quirk: JILA scientists pack atoms together to prevent collisions in atomic clock
2011-02-04
BOULDER, Colo.—In a paradox typical of the quantum world, JILA scientists have eliminated collisions between atoms in an atomic clock by packing the atoms closer together. The surprising discovery, described in the Feb. 3 issue of Science Express,* can
boost the performance of experimental atomic clocks made of thousands or tens of thousands of neutral atoms trapped by intersecting laser beams.
JILA is jointly operated by the National Institute of Standards and Technology (NIST) and the University of Colorado Boulder.
JILA scientists demonstrated the new approach using ...
Yale scientists identify a deadly tool in Salmonella's bag of tricks
2011-02-04
The potentially deadly bacterium Salmonella possesses a molecular machine that marshals the proteins it needs to hijack cellular mechanisms and infect millions worldwide.
In a paper published Feb. 3 online in Science Express, Yale University researchers describe in detail how Salmonella, a major cause of food poisoning and typhoid fever, is able to make these proteins line in up in just the right sequence to invade host cells.
"These mechanisms present us with novel targets that might form the basis for the development of an entirely new class of anti-microbials," ...
Obesity has doubled since 1980, major global analysis of risk factors reveals
2011-02-04
The study shows that in 2008, more than one in ten of the world's adult population was obese, with women more likely to be obese than men. An estimated 205 million men and 297 million adult women were obese - a total of more than half a billion adults worldwide.
The proportion of the world's population with high blood pressure, or uncontrolled hypertension, fell modestly between 1980 and 2008. However, because of population growth and ageing, the number of people with uncontrolled hypertension rose from 600 million in 1980 to nearly 1 billion in 2008. High-income countries ...
2nd member in Alzheimer's toxic duo identified
2011-02-04
SAN ANTONIO, Texas, U.S.A. (Feb. 4, 2011) — Like two unruly boys who need to be split up in class, a pair of protein molecules work together to speed up the toxic events of Alzheimer's disease. Researchers at the UT Health Science Center San Antonio today announced the discovery of the second molecule and said its identification could lead to drugs that disrupt the interaction, and thereby block or slow Alzheimer's onset or progression.
Alzheimer's disease is an irreversible, progressive brain disease marked by deterioration of nerve cells and eventual complete loss of ...
New nanomaterials unlock new electronic and energy technologies
2011-02-04
A new way of splitting layered materials to give atom thin "nanosheets" has been discovered. This has led to a range of novel two-dimensional nanomaterials with chemical and electronic properties that have the potential to enable new electronic and energy storage technologies. The collaborative* international research led by the Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Ireland, and the University of Oxford has been published in this week's Science.
The scientists have invented a versatile method for creating these ...