Most Complete Human Brain Model to Date Is a ‘Brain Changer’

Once licensed, model likely to accelerate study of Alzheimer’s, autism, more

Wednesday, 19 August 2015

Scientists at The Ohio State University have developed a nearly complete human brain in a dish that equals the brain maturity of a 5-week-old foetus.

The brain organoid, engineered from adult human skin cells, is the most complete human brain model yet developed, said Rene Anand, professor of biological chemistry and pharmacology at Ohio State.

The lab-grown brain, about the size of a pencil eraser, has an identifiable structure and contains 99 percent of the genes present in the human foetal brain. Such a system will enable ethical and more rapid and accurate testing of experimental drugs before the clinical trial stage and advance studies of genetic and environmental causes of central nervous system disorders.

“It not only looks like the developing brain, its diverse cell types express nearly all genes like a brain,” Anand said.

“We’ve struggled for a long time trying to solve complex brain disease problems that cause tremendous pain and suffering. The power of this brain model bodes very well for human health because it gives us better and more relevant options to test and develop therapeutics other than rodents.”

Anand reported on his lab-grown brain Tuesday (Aug. 18) at the 2015 Military Health System Research Symposium in Ft. Lauderdale, Florida.

This image of the lab-grown brain is labelled to

show identifiable structures: the cerebral

hemisphere, the optic stalk and the cephalic

flexure, a bend in the mid-brain region, all

characteristic of the human foetal brain. Credit:

courtesy of The Ohio State University.

Anand, who studies the association between nicotinic receptors and central nervous system disorders, was inspired to pursue a model of human neural biology after encountering disappointing results in a rodent study of an experimental autism drug. Taking a chance with a shoestring budget compared to other researchers doing similar projects, he added stem-cell engineering to his research program. Four years later, he had built himself a replica of the human brain.

The main thing missing in this model is a vascular system. What is there – a spinal cord, all major regions of the brain, multiple cell types, signalling circuitry and even a retina – has the potential to dramatically accelerate the pace of neuroscience research, said Anand, also a professor of neuroscience.

“In central nervous system diseases, this will enable studies of either underlying genetic susceptibility or purely environmental influences, or a combination,” he said.

“Genomic science infers there are up to 600 genes that give rise to autism, but we are stuck there. Mathematical correlations and statistical methods are insufficient to in themselves identify causation. You need an experimental system – you need a human brain.”

Converting adult skin cells into pluripotent cells – immature stem cells that can be programmed to become any tissue in the body – is a rapidly developing area of science that earned the researcher who discovered the technique, Shinya Yamanaka, a Nobel Prize in 2012.

“Once a cell is in that pluripotent state, it can become any organ – if you know what to do to support it to become that organ,” Anand said.

“The brain has been the holy grail because of its enormous complexity compared to any other organ. Other groups are attempting to do this as well.”

Anand’s method is proprietary and he has filed an invention disclosure with the university.

He said he used techniques to differentiate pluripotent stem cells into cells that are designed to become neural tissue, components of the central nervous system or other brain regions.

“We provide the best possible environment and conditions that replicate what’s going on in utero to support the brain,” he said of the work he completed with colleague Susan McKay, a research associate in biological chemistry and pharmacology.

High-resolution imaging of the organoid identifies functioning neurons and their signal-carrying extensions – axons and dendrites – as well as astrocytes, oligodendrocytes and microglia. The model also activates markers for cells that have the classic excitatory and inhibitory functions in the brain, and that enable chemical signals to travel throughout the structure.

It takes about 15 weeks to build a model system developed to match the 5-week-old foetal human brain. Anand and McKay have let the model continue to grow to the 12-week point, observing expected maturation changes along the way.

“If we let it go to 16 or 20 weeks, that might complete it, filling in that 1 percent of missing genes. We don’t know yet,” he said.

He and McKay have already used the platform to launch their own projects, creating brain organoid models of Alzheimer’s and Parkinson’s diseases and autism in a dish. They hope that with further development and the addition of a pumping blood supply, the model could be used for stroke therapy studies. For military purposes, the system offers a new platform for the study of Gulf War illness, traumatic brain injury and post-traumatic stress disorder.

Anand hopes his brain model could be incorporated into the Microphysiological Systems program, a platform the Defense Advanced Research Projects Agency is developing by using engineered human tissue to mimic human physiological systems.

Support for the work came from the Marci and Bill Ingram Research Fund for Autism Spectrum Disorders and the Ohio State University Wexner Medical Center Research Fund.

Anand and McKay are co-founders of a Columbus-based start-up company, NeurXstem, to commercialize the brain organoid platform, and have applied for funding from the federal Small Business Technology Transfer program to accelerate its drug discovery applications.

Source: Ohio State University

Contact: Rene Anand

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New Stem Cell May Overcome Hurdles for Regenerative Medicine

Salk Institute scientists discover new type of stem cell that could potentially generate mature, functional tissues

Thursday, 07 May 2015

In this image, a novel type of human stem cell is

shown in green integrating and developing into

the surrounding cells of a nonviable mouse

embryo. Red indicates cells of endoderm lineage.

Endoderm cells can give rise to tissue that covers

organs from the digestive and respiratory

systems. The new stem cell, developed at the

Salk Institute, holds promise for one day growing

replacement functional cells and tissues. Credit:

Courtesy of the Salk Institute for Biological

Studies.

Scientists at the Salk Institute have discovered a novel type of pluripotent stem cell – cells capable of developing into any type of tissue – whose identity is tied to their location in a developing embryo. This contrasts with stem cells traditionally used in scientific study, which are characterized by their time-related stage of development.

In the paper, published May 6, 2015 in Nature, the scientists report using these new stem cells to develop the first reliable method for integrating human stem cells into nonviable mouse embryos in a laboratory dish in such a way that the human cells began to differentiate into early-stage tissues.

“The region-specific cells we found could provide tremendous advantages in the laboratory to study development, evolution and disease, and may offer avenues for generating novel therapies,” says Salk Professor Juan Carlos Izpisua Belmonte, senior author of the paper and holder of Salk’s Roger Guillemin Chair.

The researchers dubbed this new class of cells “region-selective pluripotent stem cells,” or rsPSCs for short. The rsPSCs were easier to grow in the laboratory than conventional human pluripotent stem cells and offered advantages for large-scale production and gene editing (altering a cell’s DNA), both desirable features for cell replacement therapies.

Juan Carlos Izpisua Belmonte and Jun Wu

Credit: Courtesy of the Salk Institute for

Biological Studies.

To produce the cells, the Salk scientists developed a combination of chemical signals that directed human stem cells in a laboratory dish to become spatially oriented.

They then inserted the spatially oriented human stem cells (human rsPSCs) into specific regions of partially dissected mouse embryos and cultured them in a dish for 36 hours. Separately, they also inserted human stem cells cultured using conventional methods, so that they could compare existing techniques to their new technique.

While the human stem cells derived through conventional methods failed to integrate into the modified embryos, the human rsPSCs began to develop into early stage tissues. The cells in this region of an early embryo undergo dynamic changes to give rise to all cells, tissues and organs of the body. Indeed the human rsPSCs began the process of differentiating into the three major cell layers in early development, known as ectoderm, mesoderm and endoderm. The Salk researchers stopped the cells from differentiating further, but each germ layer was theoretically capable of giving rise to specific tissues and organs.

The new stem cell (green), developed at the Salk

Institute, holds promise for one day growing

replacement functional cells and tissues. Credit:

Courtesy of the Salk Institute for Biological

Studies.

Collaborating with the labs of Salk Professors Joseph Ecker and Alan Saghatelian, the Izpisua Belmonte team performed extensive characterization of the new cells and found rsPSCs showed distinct molecular and metabolic characteristics as well as novel epigenetic signatures – that is, patterns of chemical modifications to DNA that control which genes are turned on or off without changing the DNA sequence.

“The region selective-state of these stem cells is entirely novel for laboratory-cultured stem cells and offers important insight into how human stem cells might be differentiated into derivatives that give rise to a wide range of tissues and organs,” says Jun Wu, a postdoctoral researcher in Izpisua Belmonte’s lab and first author of the new paper.

“Not only do we need to consider the timing, but also the spatial characteristics of the stem cells. Understanding both aspects of a stem cell’s identity could be crucial to generate functional and mature cell types for regenerative medicine.”

Source: Salk Institute

Contact: Salk Communications

Reference:

An alternative pluripotent state confers interspecies chimaeric competency

Authors: Jun Wu, Daiji Okamura, Mo Li, Keiichiro Suzuki, Chongyuan Luo,Li Ma, Yupeng He, Zhongwei Li, Chris Benner, Isao Tamura, Marie N. Krause, Joseph R. Nery, Tingting Du, Zhuzhu Zhang, Tomoaki Hishida, Yuta Takahashi, Emi Aizawa, Na Young Kim, Jeronimo Lajara, Pedro Guillen, Josep M. Campistol, Concepcion Rodriguez Esteban, Pablo J. Ross, Alan Saghatelian, Bing Ren, Joseph R. Ecker and Juan Carlos Izpisua Belmonte

Nature, 06 May 2015, doi:10.1038/nature14413

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Reprogramming Cells, Long Term

Positive finding could have major implications for diabetes treatment

Tuesday, 18 November 2014

Harvard Stem Cell Institute (HSCI) researchers, representing five Harvard departments and affiliated institutions as well as the Massachusetts Institute of Technology (MIT), have demonstrated that adult cells, reprogrammed into another cell type in a living animal, can remain functional over a long period.

Joe Zhou is a Harvard Stem Cell Institute

Principal Faculty Member and an Associate

Professor in Harvard's Department of Stem Cell

and Regenerative Biology. Zhou and colleagues

have demonstrated that cells reprogrammed in

vivo can survive, thrive, and be therapeutically

useful. Credit: B. D. Colen/Harvard University.

The work by Joe Zhou, an associate professor in Harvard's Department of Stem Cell and Regenerative Biology, and his collaborators is an important advance in the effort to develop cell-based therapies for tissue repair, and specifically in the effort to develop improved treatment for diabetes.

The researchers used a combination of genes to change pancreatic exocrine cells – one of the main forms of cells in the pancreas – in adult mice that have diabetes into insulin-producing beta cells that appeared to cure about a third of the mice of the metabolic disease, and improved insulin production in most of the other mice. A report on the work was published today in the journal Nature Biotechnology.

The new findings are a major advance in work by HSCI co-director Doug Melton and Zhou, who in 2008 reported having converted exocrine cells into functional beta cells in mice. At that time, however, it was not known how long, and how well, the repurposed cells would function.

"The efficiency of reprogramming has always been an issue," Zhou said.

"Until now, the new cells have either dropped dramatically in number or disappeared completely," he said, noting that since his work with Melton in 2008 there have been reports published in other programing systems that question whether the reprogrammed cells could be stable enough ultimately to be useful.

"What we have demonstrated is that yes, the reprogrammed cells can be useful, and for that to happen you have to create a niche environment in which the cells can survive," Zhou continued.

"We have improved the reprogramming efficiency to a point where one can create a large enough number of the new cells that the new cells create their own niche environment."

Zhou said that the researchers studied the mice for up to about 13 months, approximately half their normal life span, and found that "the cells are still there, and fairly robust. These are diabetic animals, and we were able to, I wouldn't use the word 'cure' because that's a very freighted word for me to use, but they became highly glycaemic animals – though not every animal became normal. That may be because to completely control the glucose level of the animal, you not only need beta cells, you need about a quarter of a million functional beta cells. If you are short of this number, even if the beta cells are perfectly normal," they can't completely control blood sugar levels, Zhou said.

When discussing the implications of the study for the field of cellular reprogramming, Zhou cautioned that the pancreas has a particularly simple cellular organization and structure, and thus findings in the pancreas might not necessarily apply to other organs.

Diabetes is a metabolic disease that is seen in two basic forms.

Type 1 diabetes is an autoimmune disease affecting about 3 million Americans, in which the patient's immune system ultimate destroys all the insulin-producing beta cells in the pancreas, and the patient has to inject insulin in order to regulate blood glucose levels.

Type 2 diabetes, which is now at epidemic prevalence rates in the United States and around the world, is usually caused by being overweight, lack of proper exercise, and improper diet, and can make a patient insulin-resistant, so the insulin the body produces is not sufficient to control blood glucose levels.

If the kind of treatment approach suggested by the new study were to succeed in humans – and that is a question to be answered with further animal, and eventually human, studies – it could be useful in treating both forms of diabetes.

One drawback to the current form of the new approach is that the cellular reprogramming is done with genes, and there might ultimately be unwanted effects on the cells. Zhou said the goal would be to replace the genes with chemicals or, perhaps, RNAs.

"I've talked to many clinicians about whether our approach could be used in humans," Zhou said.

"And the opinion is divided. Some say this could be developed into a human treatment, and some say it should be improved. But there seems to be general agreement that it could potentially be useful."

Source: Harvard University

Contact: B. D. Colen

Reference:

Long-term persistence and development of induced pancreatic beta cells generated by lineage conversion of acinar cells

Weida Li, Claudia Cavelti-Weder, Yinying Zhang, Kendell Clement, Scott Donovan, Gabriel Gonzalez, Jiang Zhu, Marianne Stemann, Ke Xu, Tatsu Hashimoto, Takatsugu Yamada, Mio Nakanishi, Yuemei Zhang, Samuel Zeng, David Gifford, Alexander Meissner, Gordon Weir & Qiao Zhou

Nature Biotechnology (2014), doi:10.1038/nbt.3082

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Shopping for an Egg Donor

Is beauty, brains, or health most important?

Tuesday, 21 October 2014

Human egg cell. 

When it comes to picking an egg donor, until recent years, recipients tended to prefer someone with a similar appearance. Donor trait choices are changing, though, and which traits are now more preferable and why is the focus of "Beauty, Brains or Health: Trends in Ovum Recipient Preferences," an article published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website at http://online.liebertpub.com/doi/full/10.1089/jwh.2014.4792 until November 20, 2014.

Homero Flores, MD and coauthors from Reproductive Medicine Associates of New York and Icahn School of Medicine at Mount Sinai (New York, NY) reviewed the requests of ovum donor recipients over a 5-year period and assessed their preferences for donor traits, categorizing them by appearance, ethnicity, intellect, ability, and mental health. The authors documented statistically significant increases and decreases in the different categories over the years, with more "practical traits" that would improve offspring's overall quality of life tending to increase compared to "self-reflective" traits.

"As social acceptance of ovum donation has increased, and donor selection has become more sophisticated, couples are changing their preferences for what donor characteristics they value most for their future offspring," says Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health.

Source: Mary Ann Liebert, Inc./Genetic Engineering News

Contact: Kathryn Ryan

Reference:

Beauty, Brains or Health: Trends in Ovum Recipient Preferences

Flores Homero, Lee Joseph, Rodriguez-Purata Jorge, Witkin Georgia, Sandler Benjamin, and Copperman Alan B.

Journal of Women's Health. October 2014, 23(10): 830-833. doi:10.1089/jwh.2014.4792

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Stem Cell Success Raises Hopes of Type 1 Diabetes Cure

From human embryonic stem cells to billions of human insulin producing cells

Giant step toward new diabetes treatment

Friday, 10 October 2014

This is an image of human stem cell-derived beta

cells that have formed islet like clusters in a

mouse. Cells were transplanted to the kidney

capsule and photo was taken two weeks later by

which time the beta cells are making insulin and

have cured the diabetes in the mouse. Credit:

Douglas Melton. 

Harvard stem cell researchers today announced that they have made a giant leap forward in the quest to find a truly effective treatment for type 1 diabetes, a condition that affects an estimated three million Americans at a cost of about $15 billion annually: With human embryonic stem cells as a starting point, the scientists are for the first time able to produce, in the kind of massive quantities needed for cell transplantation and pharmaceutical purposes, human insulin-producing beta cells equivalent in most every way to normally functioning beta cells.

Doug Melton, who led the work and who twenty-three years ago, when his then infant son Sam was diagnosed with type 1 diabetes, dedicated his career to finding a cure for the disease, said he hopes to have human transplantation trials using the cells to be underway within a few years.

"We are now just one pre-clinical step away from the finish line," said Melton, whose daughter Emma also has type 1 diabetes.

A report on the new work has today been published by the journal Cell.

Felicia W. Pagliuca, Jeff Millman, and Mads Gurtler of Melton's lab are co-first authors on the Cell paper. The research group and paper authors include a Harvard undergraduate.

"You never know for sure that something like this is going to work until you've tested it numerous ways," said Melton, Harvard's Xander University Professor and a Howard Hughes Medical Institute Investigator.

"We've given these cells three separate challenges with glucose in mice and they've responded appropriately; that was really exciting.”

"It was gratifying to know that we could do something that we always thought was possible," he continued, "but many people felt it wouldn't work. If we had shown this was not possible, then I would have had to give up on this whole approach. Now I'm really energized."

The stem cell-derived beta cells are presently undergoing trials in animal models, including non-human primates, Melton said.

Elaine Fuchs, the Rebecca C. Lancefield Professor at Rockefeller University, and a Howard Hughes Medical Institute Investigator who is not involved in the work, hailed it as "one of the most important advances to date in the stem cell field, and I join the many people throughout the world in applauding my colleague for this remarkable achievement.”

"For decades, researchers have tried to generate human pancreatic beta cells that could be cultured and passaged long term under conditions where they produce insulin. Melton and his colleagues have now overcome this hurdle and opened the door for drug discovery and transplantation therapy in diabetes," Fuchs said.

And Jose Oberholtzer, M.D., Associate Professor of Surgery, Endocrinology and Diabetes, and Bioengineering at the University of Illinois at Chicago, and its Director of the Islet and Pancreas Transplant Program and the Chief of the Division of Transplantation, said work described in today's Cell "will leave a dent in the history of diabetes. Doug Melton has put in a life-time of hard work in finding a way of generating human islet cells in vitro. He made it. This is a phenomenal accomplishment."

Doug Melton, who when his then infant son was

diagnosed 23 years ago with type 1 diabetes

dedicated his career to finding a cure for the

disease, has successfully produced insulin

producing, glucose sensitive, human beta cells

from human embryonic stem cells. Credit: B. D.

Colen/Harvard University.

Melton, co-scientific director of the Harvard Stem Cell Institute, and the University's Department of Stem Cell and Regenerative Biology – both of which were created more than a decade after he began his quest – said that when he told his son and daughter they were surprisingly calm.

"I think like all kids, they always assumed that if I said I'd do this, I'd do it," he said with a self-deprecating grin.

Type 1 diabetes is an autoimmune metabolic condition in which the body kills off all the pancreatic beta cells that produce the insulin needed for glucose regulation in the body. Thus the final pre-clinical step in the development of a treatment involves protecting from immune system attack the approximately 150 million cells that would have to be transplanted into each patient being treated. Melton is collaborating on the development of an implantation device to protect the cells with Daniel G. Anderson, the Samuel A. Goldblith Professor of Applied Biology, Associate Professor in the Department of Chemical Engineering, the Institute of Medical Engineering and Science, and the Koch Institute at MIT.

Melton said that the device Anderson and his colleagues at MIT are currently testing has thus far protected beta cells implanted in mice from immune attack for many months.

"They are still producing insulin," Melton said.

Cell transplantation as a treatment for diabetes is still essentially experimental, uses cells from cadavers, requires the use of powerful immunosuppressive drugs, and has been available to only a very small number of patients.

MIT's Anderson said the new work by Melton's lab is "an incredibly important advance for diabetes. There is no question that ability to generate glucose-responsive, human beta cells through controlled differentiation of stem cells will accelerate the development of new therapeutics. In particular, this advance opens doors to an essentially limitless supply of tissue for diabetic patients awaiting cell therapy."

Richard A. Insel, M.D., chief scientific officer of the Juvenile Diabetes Research Foundation, a founder of Melton's work, said the "JDRF is thrilled with this advancement toward large scale production of mature, functional human beta cells by Dr. Melton and his team. This significant accomplishment has the potential to serve as a cell source for islet replacement in people with type 1 diabetes and may provide a resource for discovery of beta cell therapies that promote survival or regeneration of beta cells and development of screening biomarkers to monitor beta cell health and survival to guide therapeutic strategies for all stages of the disease."

Melton expressed gratitude to both the Juvenile Diabetes Research Foundation and the Helmsley Trust, saying "their support has been, and continues to be essential."

While diabetics can keep their glucose metabolism under general control by injecting insulin multiple times a day, that does not provide the kind of exquisite fine tuning necessary to properly control metabolism, and that lack of control leads to devastating complications from blindness to loss of limbs.

About 10 percent of the more than 26 million Americans living with type 2 diabetes are also dependent upon insulin injections, and would presumably be candidates for beta cell transplants, Melton said.

"There have been previous reports of other labs deriving beta cell types from stem cells, no other group has produced mature beta cells as suitable for use in patients," he said.

"The biggest hurdle has been to get to glucose sensing, insulin secreting beta cells, and that's what our group has done."

Source: Harvard University

Contact: B. D. Colen

Reference:

Generation of Functional Human Pancreatic β Cells In Vitro

Felicia W. Pagliuca, Jeffrey R. Millman, Mads Gürtler, Michael Segel, Alana Van Dervort, Jennifer Hyoje Ryu, Quinn P. Peterson, Dale Greiner, Douglas A. Melton

Cell, 9 October 2014, Volume 159, Issue 2, p428–439

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New Material Could Enhance Fast and Accurate DNA Sequencing

New Material Could Enhance Fast and Accurate DNA Sequencing

Wednesday, 13 August 2014

Gene-based personalized medicine has many possibilities for diagnosis and targeted therapy, but one big bottleneck: the expensive and time-consuming DNA-sequencing process.

A DNA molecule passes through a nanopore in a

sheet of molybdenum disulphide, a material that

researchers have found to be better than

graphene at reading the DNA sequence. 

Credit: Narayana Aluru, University of Illinois.

Now, researchers at the University of Illinois at Urbana-Champaign have found that nanopores in the material molybdenum disulphide (MoS2) could sequence DNA more accurately, quickly and inexpensively than anything yet available.

"One of the big areas in science is to sequence the human genome for under $1,000, the 'genome-at-home,'" said Narayana Aluru, a professor of mechanical science and engineering at the U. of I. who led the study.

"There is now a hunt to find the right material. We've used MoS2 for other problems, and we thought, why don't we try it and see how it does for DNA sequencing?"

As it turns out, MoS2 outperforms all other materials used for nanopore DNA sequencing – even graphene.

A nanopore is a very tiny hole drilled through a thin sheet of material. The pore is just big enough for a DNA molecule to thread through. An electric current drives the DNA through the nanopore, and the fluctuations in the current as the DNA passes through the pore tell the sequence of the DNA, since each of the four letters of the DNA alphabet – A, C, G and T – are slightly different in shape and size.

Illinois researchers found that the material

molybdenum disulphide could be the most

efficient yet found for DNA sequencing, making

personalized medicine more accessible. From

left: Amir Barati Farimani, Kyongmin Min and

Narayana Aluru. Credit: L. Brian Stauffer.

Most materials used for nanopore DNA sequencing have a sizable flaw: They are too thick. Even a thin sheet of most materials spans multiple links of the DNA chain, making it impossible to accurately determine the exact DNA sequence.

Graphene has become a popular alternative, since it is a sheet made of a single layer of carbon atoms – meaning only one base at a time goes through the nanopore. Unfortunately, graphene has its own set of problems, the biggest being that the DNA sticks to it. The DNA interacting with the graphene introduces a lot of noise that makes it hard to read the current, like a radio station marred by loud static.

MoS2 is also a single-layer sheet, thin enough that only one DNA letter at a time goes through the nanopore. In the study, the Illinois researchers found that DNA does not stick to MoS2, but threads through the pore cleanly and quickly. See an animation online.

"MoS2 is a competitor of graphene in terms of transistors, but we showed here a new functionality of this material by showing that it is capable of biosensing," said graduate student Amir Barati Farimani, the first author of the paper.

Most exciting for the researchers, the simulations yielded four distinct signals corresponding to the bases in a double-stranded DNA molecule. Other systems have yielded two at best – A/T and C/G – which then require extensive computational analysis to attempt to distinguish A from T and C from G.

The key to the success of the complex MoS2 simulation and analysis was the Blue Waters supercomputer, located at the National Center for Supercomputing Applications at the U. of Illinois.

"These are very detailed calculations," said Aluru, who is also a part of the Beckman Institute for Advanced Science and Technology at the U. of I.

"They really tell us the physics of the actual mechanisms, and why MoS2 is performing better than other materials. We have those insights now because of this work, which used Blue Waters extensively."

Now, the researchers are exploring whether they can achieve even greater performance by coupling MoS2 with another material to form a low-cost, fast and accurate DNA sequencing device.

"The ultimate goal of this research is to make some kind of home-based or personal DNA sequencing device," Barati Farimani said.

"We are on the path to get there, by finding the technologies that can quickly, cheaply and accurately identify the human genome. Having a map of your DNA can help to prevent or detect diseases in the earliest stages of development. If everybody can cheaply sequence so they can know the map of their genetics, they can be much more alert to what goes on in their bodies."

Source: University of Illinois at Urbana-Champaign 

Contact: Liz Ahlberg

Reference:

DNA Base Detection Using a Single-Layer MoS2

Amir Barati Farimani, Kyoungmin Min, and Narayana R. Aluru 

ACS Nano, July 9, 2014, DOI: 10.1021/nn5029295

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Researchers Create 'Naïve' Pluripotent Human Embryonic Stem Cells

Researchers Create 'Naïve' Pluripotent Human Embryonic Stem Cells

Saturday, 26 July 2014

Phase and fluorescence images of conventional

(primed) human embryonic stem cells (ESCs)

and naïve human ESCs generated in the

presence of 5 small molecule inhibitors.

The naïve human ESCs exhibit activation of a

fluorescent reporter linked to an enhancer of

theOCT4 gene that is specifically used in

the naïve state. 40X magnification. Credit:

Courtesy of Thorold Theunissen. 

For years, researchers and patients have hoped that embryonic stem cells (ESCs) — capable of forming nearly any cell type in the body — could provide insight into numerous diseases perhaps even be used to treat them. Yet progress has been hampered by the inability to transfer research and tools from mouse ESC studies to their human counterparts, in part because human ESCs are "primed" and slightly less plastic than the mouse cells.

Now Thorold Theunissen, Benjamin Powell, and Haoyi Wang, who are scientists in the lab of Whitehead Institute Founding Member Rudolf Jaenisch, have discovered how to manipulate and maintain human ESCs in a "naïve" or base pluripotent state similar to that of mouse ESCs without the use of any reprogramming factors. Their work is described in this week's issue of the journal Cell Stem Cell.

Naïve mice ESCs are well-studied, and scientists have a strong understanding of how they function and mature into more specialized cells. But this understanding is of limited use in human ESC research, as the human cells look different, grow differently, and rely on different genes than mouse ESCs. According to Theunissen, the disparities between mouse and human ESCs are attributable not to species-specific differences but rather to differences of cell state.

In naïve mouse ESCs, a particular enhancer of the gene OCT4 is active, prompting the researchers to look for the presence of this marker as a means to identify rare naïve human ESCs. With this unbiased reporter system in hand, the Jaenisch team determined that a cocktail of five small molecules with a few additional growth factors can induce and support the conversion of primed human ESCs to a naïve state with or without using reprogramming factors to jumpstart the process.

By applying this cocktail to human blastocysts, the scientists could also isolate naïve human stem cells.

"This is important because if this cocktail only works in existing lines of human ESCs, you might wonder, does this really capture a distinct state or is this artificial?" says Theunissen.

"Since the cocktail works directly on human blastocysts, I think it suggests that we're really capturing a cell state that is already present in the early human embryo."

Although other labs have recently reported creating naïve human ESCs, Theunissen, Powell, and Wang question these results as the cells produced through these techniques lack the gene expression and epigenetic profiles of naïve human ESCs. Yet, the Jaenisch lab believes they have now finally unlocked a way to create and maintain this important type of cell and are looking forward to exploring its potential.

"We have discovered a new pathway to generate something we believe is a totally different state of pluripotency in human ESCs that is very close to the mouse naïve state," says Jaenisch, who is also a professor of biology at MIT.

"These cells may be essential for ESC technology, and that is an area we're looking forward to investigating. Now the big question for us is, does this state exist in vivo in embryos? Right now, we don't know, and that is a very interesting line of research."

Source: Whitehead Institute for Biomedical Research 

Contact: Nicole Giese Rura

Reference:

Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency

Thorold W. Theunissen, Benjamin E. Powell, Haoyi Wang, Maya Mitalipova, Dina A. Faddah, Jessica Reddy, Zi Peng Fan, Dorothea Maetzel, Kibibi Ganz, Linyu Shi, Tenzin Lungjangwa, Sumeth Imsoonthornruksa, Yonatan Stelzer, Sudharshan Rangarajan, Ana D'Alessio, Jianming Zhang, Qing Gao, Meelad M. Dawlaty, Richard A. Young, Nathanael S. Gray, and Rudolf Jaenisch

Cell Stem Cell, July 24, 2014, http://www.cell.com/cell-stem-cell/abstract/S1934-5909(14)00298-7

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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Umbilical Cord Blood, at the Cutting Edge of Today’s Medicine

“Saving Grace”

From: Al Jazeera America’s TECHKNOW Presents

Thursday, 17 July 2014

This Saturday, July 19th at 7:30 pm ET/4:30 pm PT, Al Jazeera America’s “TechKnow” shows us one of the most exiting areas of medical research – how umbilical cord blood is being used to treat brain disease and injury.

Dr. Joanne Kurtzberg. Credit: Al Jazeera.

“Techknow” host and mechanical engineer Dr. Shini Somara takes us inside Duke Children’s Hospital, where a team of doctors is treating young Grace Matthews, an infant with hydrocephalus, or water on the brain, characterized by the tell-tale swelling of the baby’s head.  We go behind-the-scenes on the high-tech experimental treatments, as doctors infuse Grace with stem cells from her own umbilical cord, and we meet another young patient who experienced “miraculous” progress from the use of umbilical cord stem cells.

The medical equivalent of gold, we’re just at the tip of understanding how stem cells from cord blood, harvested at the time of birth, can be used to help the brain regenerate and heal from injuries and damage.

“I personally believe cell therapy, and regenerative medicine, is going to be the next big advance in medicine, and that cells like cord blood are going to drive that forward,” reports Dr. Joanne Kurtzberg, Chief of the Division of Pediatric Blood and Marrow Transplantation at Duke University Medical Center in Durham, North Carolina.

The program is airing Saturday, July 19th at 7:30PET/4:30P PT;

Repeats 10:30P ET/7:30P PT

Find Al Jazeera America near you: www.aljazeera.com/getajam

About Al Jazeera America’s “TechKnow”:

Al Jazeera America’s “TechKnow” is a half hour documentary show that airs weekly on Saturdays at 7:30 pm ET/4:30 pm PT.  A show about innovations that can change lives, “TechKnow” explores the intersection of hardware and humanity in a unique way – it’s a show about science, by scientists. “TechKnow” rotating cast of hosts includes mechanical engineer Dr. Shini Somara, molecular neuroscientist Dr. Crystal Dilworth, entolomologist Phil Torres, biologist Marita Davison, engineer Kosta Grammatis, science writer Kyle Hill, former CIA operative and analyst Lindsay Moran, neuroscientist Rachelle Oldmixon and neurobiologist Cara Santa Maria.

Source: Al Jazeera America’s “TechKnow”

Contact: Jocelyn Austin, Director, Publicity

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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