University study sheds light on human embryonic stem cells’ DNA changes
****Images available***
A study on the genome of human embryonic stem cells
(hESCs) has brought scientist closer to identify and circumvent the adverse DNA
changes that naturally occur when these cells are multiplied in laboratory. The
findings could help researchers to prevent deleterious mutations in cultured
hESCs- a factor that hampers their future medical use – advancing towards application
of stem-cells-based regenerative treatments.
The collaborative study, coordinated through EU-funded
project ESTOOLS and involving experts at the University of Sheffield, is published
by the peer-review journal Nature Biotechnology, and appeared on the journal’s website on March 29th. [note: add complete reference to the article with DOI: 10.1038/nbt.1615]
Embryonic stem cells are studied for potential applications
in regenerative cell replacement therapies because of their unique capacity to
self-renew and differentiate into a variety of cell and tissue types, including
neurons, blood cells, bone and muscle.
However, it is known that genetic changes take place
in various hESC lines as they are kept multiplying in laboratory, some of which
resemble the DNA abnormalities typical of cancer cells. hESCs may also undergo
other genetic changes undetectable by conventional methods, raising concerns
for their medical use.
To address this issue, researchers used high
resolution DNA analysis to plot the genetic changes in 17 hESC lines cultured
over many generations, from the ESTOOLS consortium, the largest cluster of hESCs
laboratories in Europe. Authors of the study include several partners of ESTOOLS consortium,
including Prof Riitta Lashema and colleagues in Turku, Finland.
The study (which is the highest-resolution DNA
analysis ever done on hESCs genome) mapped hundreds
of copy number variations (CNV) and loss of heterozigosity (LOH)after prolonged
passages in culture. Both CNV and LOH are genetic variations that are usually associated with tumour transformation.
For the first time, researchers could shortlist a
number of genes that map inside or near the mutated sites, and that could therefore
be affected by these potentially deleterious changes. “When we know which genes are involved, it will be easier
to reject those hESC lines in which those genes are mutated”, says
Peter W. Andrews, from the University’s Department of Biomedical Sciences, a
leading author of the study.
Importantly, researchers found
that some hESC lines are significantly less prone to undergo genetic abnormalities
than others, which will help to select
lines that are more suitable for medical applications.
Authors point out that the
study will also help to dig into the so-called culture adaptation process, i.e.
the accumulation of genetic changes typical of malignant transformation, that
is mimicked by hESCs in culture.
Notes for editors:
For more information on
the ESTOOLS International Scientific Symposium, please visit:
Study from NeuroStemcell group opens new perspectives for Parkinson’s
November 6th, 2011
A study coordinated by Lorenz Studer, a NEUROSTEMCELL principal investigator, has developed a new strategy for the efficient transformation of human pluripotent stem cells (PSCs) into dopamine-producing neurons. The neurons can be implanted into animals where they show “robust performance” by forming new connections and achieving long-term survival. The result is a significant progress in the use of PSCs and may help to develop new therapies for neurodegenerative diseases. The work is published in the journal Nature.
The degeneration of dopamine-producing (dopaminergic, in jargon) neurons is the main event behind the onset of Parkinson disease. One goal of NEUROSTEMCELL is to use PSCs to produce dopaminergic neurons that may be transplanted in patients affected by Parkinson’s and other neurodegenerative disorders.
Over the last decade, several groups have obtained dopaminergic-like cells from embryonic stem cells in a culture dish. However, those cells fell short of behaving like normal dopaminergic neurons. For example, they did not survive long enough after transplantation and often multiplied abnormally, leading to neural overgrowth and, sometimes, cancer.
Studer and his coworkers harnessed insights from developmental biology to overcome these problems. They developed a strategy to obtain “authentic” dopaminergic cells that are very similar to the ones normally found in the brain.
When researchers implanted these new cells into animal models of Parkinson disease — mice, rats and monkeys — the neurons survived and integrated properly in the brains, and produced dopamine like their normal counterparts. Also, they did not multiply abnormally after transplantation, which avoided neural overgrowth and adverse events following engraftment in the animals. The treatment also improved some symptoms in Parkinson’s affected rodents.
The results are encouraging but are still in the field of basic research, warn the authors of the Nature study. More work is needed before these findings may be eventually transferred to patients. “We are now gearing up to produce dopaminergic cells under conditions that would be suitable for clinical use. The process involves careful adaptations in cell manufacturing, scale up and safety testing. We expect completion of those studies within the next 3-4 years, the minimum time frame required for initiating studies potentially in human patients”, says Studer.
“We are very fortunate to be the only non-EU member of Neurostemcell […]. My lab has greatly benefited from the collaborative and interactive environment, and the shared mission helped in driving the project forward”, he says.
Sonja Kriks, Jae-Won Shim, Jinghua Piao, Yosif M. Ganat, Dustin R. Wakeman, Zhong Xie, Luis Carrillo-Reid, Gordon Auyeung, Chris Antonacci, Amanda Buch, Lichuan Yang, M. Flint Beal, D. James Surmeier, Jeffrey H. Kordower, Viviane Tabar & Lorenz Studer. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature, 6 November 2011 (online) doi:10.1038/nature10648
http://www.neurostemcell.org
Some comments from other NeuroStemcell members
Elena Cattaneo, University of Milan, NeuroStemcell coordinator:
This work represents an important step towards the possible application in the clinic of human embryonic stem cell based therapies and sets a challenge for Europe concerning the future regulatory ground and the competitiveness of regenerative medicine.
Anders Björklund, Lund University, Sweden and NeuroStemcell deputy coordinator:
The new study represents an important step in the development of a stem cell based therapy for Parkinson´s disease. Efforts along these lines go back to the late 1980s when the first patients received transplants of dopamine neurons derived from the developing brain of aborted fetuses. Although these trials have given quite promising results in some patients, the use of fetal tissue for cell transplantation is both ethically and practically problematic. Over the last decade, therefore, the focus of research has been on the use of stem cells for this purpose. The generation of fully functional dopamine neurons in large numbers, however, has turned out to be a challenge. Previous attempts have faced two major hurdles: to get the stem cell derived dopamine neurons to survive and grow in the recipient brain, and to avoid the inclusion of dividing cells that overgrow to form tumors. The derivation technique devised by the Studer team in this new study is a breakthrough in this regard: their procedure is not only remarkably efficient, but the neurons generated show excellent survival and provide efficient restoration of motor deficits in both rodent and primate transplantation models.
Austin Smith, University of Cambridge, NeuroStemcell PI:
The European Commission have played an important role by part-funding the research. This means the results have been shared at an early stage with European scientists who are now working towards applications in patients together with Dr Studer.
Of the many dog DNA tests on the market, which one is right for you and your pet? How do they work, are they accurate, and what can you learn?
For the genealogically curious, DNA tests are increasingly popular as holiday gifts, and this is not just limited to test kits for humans: Dog DNA tests are now available to give you insights into your pooch’s genetic makeup.
While genetic testing for human ancestry and disorders has been around for several years, dog DNA tests that can identify the breed of your four-legged-friend have appeared relatively recently. So, should pet owners invest their hard-earned money in a dog DNA test, and what can they actually reveal?
(Article featuring an interview with Sergio Pistoi about his book DNA NATION)
Exactly how accurate are DNA tests, and how much can your genetic data really reveal about you? To find out, we asked a molecular biologist.
With genetic testing for health, ancestry, paternity and more becoming increasingly popular, many people are left wondering: exactly how accurate are DNA tests? Whether you are taking a DNA test to build your extended DNA family tree with an AncestryDNA(opens in new tab) testing kit, or want precise information on hereditary health conditions with 23andMe(opens in new tab), it is important to understand how accurate genetic tests are, and what information we can rely upon.
How accurate DNA tests are relies greatly upon the kind of test being taken. “The accuracy of results depends on the specific question we ask, and on how complex is the genetics behind a trait,” Sergio Pistoi, a molecular biologist and author of “DNA Nation(opens in new tab)” (Crux Publishing, 2019), told Live Science. For example, tests for traits that depend on a single gene, called monogenic traits, provide much more reliable results, because you can see whether a disease-causing mutation or another trait is present. Read Full Article: https://www.livescience.com/how-accurate-are-dna-tests
Paul Levinson interviews Sergio Pistoi about his book
It was a great honor to be interviewed about my book DNA NATION by Paul Levinson, a writer of over 20 science fiction books and a media professor at Fordham University. We discussed about the rise of DNA social networks and the pervasive future of genetics with a little help from H.G. Wells, Spielberg and Netflix. Enjoy the interview like we did -and share!
Even with the advent of vaccines, strategies for rapid and affordable testing for COVID-19 are still paramount. The lack of evidence that the current vaccines can completely stop people from being infected and the emergence of virus variants make widespread testing crucial. But what do we mean as a “rapid” test and how do they compare to “standard” ones?
Remember that when you buy one of those genome testing kits—and eventually, you will
Sergio Pistoi
When I was a young student in Paris, the City of Love, girls at parties would what I did for a living. I still recall their unsettled looks when I answered “molecular biologist,” which would send them running to powder their noses. They never came back. Back in the early 2000s, the only people who could get stuck in a dreary conversation about DNA, Mendel’s peas and alleles were four-eyed genetic nerds who wasted their lives in laboratories. We were undateable, and the level of endogamy amongst us was startling.
Today, the tables have turned. Millions of people are spitting into a tube to get their genes analyzed and share the results on social networks. Genealogy websites, the second-most visited category in the U.S. after porn, are full of enthusiasts discussing chromosome markers like they were at a laboratory meeting. Celebrities get their genes tested during talk shows, and YouTubers upload videos on their spit-into-the-tube experience. Everyone is hungry to learn about their DNA. DNA has become trendy, my social life has significantly improved, and it’s a wonderful time to be a genetic nerd.
Much of the credit goes to direct-to-consumer genomics for shifting the public perception of DNA from “boring stuff” to fascinating, personal journey. Reading our DNA and using it online is incredibly informative and fun, and these tools have engaged the public into genetics to a level that science writers could have only dreamed of. To write my book DNA Nation I tried out at least two dozen applications where I could use my DNA file.
With the pervasive success of this technology, however, also comes a reality distortion field. In the enthusiasm surrounding the progress of genomics, we end up overstating the real nature of our DNA and believing that it is more important than it is. The Oscar for Genetic Ravings goes to Advanced Technologies, an Indian DNA company whose website claims that genetic code is a “Divine Writing,” but genetic determinism—the idea that DNA will determine our fate and identity—is deeply ingrained in our culture. Make a Google search, and you’ll find hundreds of sources (including textbooks and leading scientists) describing DNA as the blueprint of life. It would be a great, easy-to-understand analogy, if it wasn’t wrong and outdated.
DNA is not a blueprint: it’s a recipe coding for thousands of different proteins that interact with each other and with the environment, just like the ingredients of a cake in an oven. Whereas a blueprint is an exact, drawn-to-scale copy of the final product, a recipe is just a loose plot that leaves much more room to uncertainty. Open a packet of cookies: each one was made from the same recipe and baked in the same conditions, but there are no two that are identical. Look closely, and you’ll spot hundreds of little differences: a burn here, a chocolate chip there, bumps and lumps appearing in distinct places, all because of chaotic interactions between the ingredients and the environment.
Take two identical twins: they share the same DNA, and their embryos developed side-by-side in the same uterus. Yet, they have different tastes, characters and attitudes, and make different choices in life. When you read the DNA of twins, you find a duplicate copy of the same recipe, but two distinct personalities. Not what you would call a fixed plan.
We do not inherit specific instructions on how to build a cell or an organ. Our DNA contains a list of biochemical ingredients (the proteins coded in the genes) and the basic rules for their assembly (some proteins are labeled as “master” and can control the activity of others, while others can start a dominolike cascade of events) but the pieces self-organize into biochemical pathways, cells and tissues without reading a manual. The genetic recipe for a cat will not give an elephant, but you can’t read the DNA of an individual and see a Mini-Me of his features.
The long-standing blueprint analogy, with its attached determinism, is a toxic meme we have to fight in the era of genetic consumerism. As long as people will believe that our identity and fate is programmed into their DNA, there will be a market for questionable genetic tests aimed at predicting intelligence, music, reading and math abilities, and even sexual preferences.
DNA testing for talents is especially thriving in China, where the one-child policy in place for decades and a rampant economy have put an enormous pressure on parents to give their offspring a competitive edge. Local clinics offering these tests proliferate, and thousands of Chinese parents are taking into account the results of DNA analyses before selecting a school for their child. Blinded by the blueprint rhetoric, these people believe themselves to be in the vanguard of a new approach in parenting, while they are being bamboozled into costly and inaccurate tests that their children will probably throw in their teeth one day.
Make no mistake: some traits are indeed genetically programmed, and some diseases are deterministic: people with a pathogenic mutation in the CFTR gene will develop cystic fibrosis regardless of their lifestyle. Even abilities once considered only a matter of upbringing like language, abstract thinking and many behavioral traits have a significant genetic component. But it doesn’t mean that DNA always has the upper hand. The opposite is true: an overwhelming majority of our traits depend on the blending of many genetic and nongenetic factors and therefore are hard to predict from DNA.
If we are a slow-baking cake, the world surrounding us is a capricious oven changing every minute. Science can peek through the glass and check if something looks funny inside the oven, but it cannot predict what our life, experiences and luck will bring tomorrow and the day after tomorrow.
Powered by petabytes of data and intelligent algorithms, the genetic profiles of the future will be mighty, and their breadth will be frightening. Yet, no test will ever be able to predict our personalities accurately, not to mention our fates, because a significant part of what we are is not written into DNA.
When the postman knocks at your door with the DNA kit you bought online (because you will definitely buy one eventually), promise to relax for a minute and repeat to yourself: “DNA is not a blueprint. And my genes are not destiny.”
Using naked boobs to disseminate science? The Tumblr blog Boobs for Science has just proved it’s no joke. The blog requires volunteers to send photos of themselves naked or wearing underwear, together with a sign featuring a scientific statement of their choice. Some pictures are then published with a concise scientific explanation on the chosen topic.
The initiative was born in Italy, where the parent blog Tette per la Scienza has already made a splash and the Facebook page has gathered more than 20,000 fans since late October 2014. Following a few complaints of sexism, the blog has also started to welcome photos of male models.
It’s easy to get attention with naked bodies on the internet, but the blog is not just another click bait: its goal is actually to foster discussion about scientific topics. Does it actually work to engage people in science?
I spoke on the phone with Lara Tait, a 30-years old web marketer with a background in paleoanthropology. She created the blog together with her boyfriend from Milan, Italy. Below is an edited version of our interview:
Read on for my full written review and, yes, other spicy photos.
In the successful Italian comedy, Smetto quando voglio (I can quit whenever I want), a group of young and talented scholars with no career perspective turns into a successful drug-dealing mob. The story is imaginary—a surreal rendition of Breaking Bad—but it is also the portrait of Italian academia.There, the shortage of funds, baronies, and scant meritocracy hamper the careers of many endowed scientists. This fiction is not that far from reality.
Now, as an attempt to change their working conditions, Italian researchers are planning a protest movement in October, to take a stand against budget cuts and political apathy. There is no doubt that such movement is justified, but there is also a need for academics to run their universities better.