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News Article | May 19, 2017
Site: www.biosciencetechnology.com

Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a robust, efficient method for deriving microglia, the immune cells of the brain, from human stem cells. Microglia are increasingly implicated in neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis, among many others. However, research into the role of human microglia in these disorders has long been hampered by the inability to obtain them from the human nervous system. This new protocol now enables scientists around the world to generate this critical cell type from individual patients and improve our understanding of the role of microglia neurological malfunction. "NYSCF's mission is to bring cures to patients faster," said Susan L. Solomon, CEO and co- founder of NYSCF. "One way we work towards this goal is by developing methods and models that lift the entire field of stem cell research. This new protocol is the perfect example of the type of method that will enable researchers around the world to accelerate their work." Published in Stem Cell Reports, this microglia protocol is optimized for use in high-throughput experiments, such as drug screening and toxicity testing among other large-scale research applications, and has the benefit of allowing such experiments to be carried out on multiple patient samples. The scientists determined that the protocol is robust and reproducible, generating microglia from sixteen induced pluripotent stem (iPS) cell lines, stem cells that are created from individual patients. Microglia from humans have long been a desired research model, but are difficult to obtain for laboratory experiments. The NYSCF protocol provides a new source of human microglia cells, which can be generated from disease patient samples and will complement studies in mouse models to better understand the role of microglia in health and disease. Microglia generated by the NYSCF protocol will thus provide a critical tool to investigate microglia dysfunction in central nervous system disorders and advance complex disease modeling in a dish.


Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a robust, efficient method for deriving microglia, the immune cells of the brain, from human stem cells. Microglia are increasingly implicated in neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis, among many others. However, research into the role of human microglia in these disorders has long been hampered by the inability to obtain them from the human nervous system. This new protocol now enables scientists around the world to generate this critical cell type from individual patients and improve our understanding of the role of microglia neurological malfunction. "NYSCF's mission is to bring cures to patients faster," said Susan L. Solomon, CEO and co- founder of NYSCF. "One way we work towards this goal is by developing methods and models that lift the entire field of stem cell research. This new protocol is the perfect example of the type of method that will enable researchers around the world to accelerate their work." Published in Stem Cell Reports, this microglia protocol is optimized for use in high-throughput experiments, such as drug screening and toxicity testing among other large-scale research applications, and has the benefit of allowing such experiments to be carried out on multiple patient samples. The scientists determined that the protocol is robust and reproducible, generating microglia from sixteen induced pluripotent stem (iPS) cell lines, stem cells that are created from individual patients. Microglia from humans have long been a desired research model, but are difficult to obtain for laboratory experiments. The NYSCF protocol provides a new source of human microglia cells, which can be generated from disease patient samples and will complement studies in mouse models to better understand the role of microglia in health and disease. Microglia generated by the NYSCF protocol will thus provide a critical tool to investigate microglia dysfunction in central nervous system disorders and advance complex disease modeling in a dish.


New York, NY (May 18, 2017) - Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a robust, efficient method for deriving microglia, the immune cells of the brain, from human stem cells. Microglia are increasingly implicated in neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis, among many others. However, research into the role of human microglia in these disorders has long been hampered by the inability to obtain them from the human nervous system. This new protocol now enables scientists around the world to generate this critical cell type from individual patients and improve our understanding of the role of microglia neurological malfunction. "NYSCF's mission is to bring cures to patients faster," said Susan L. Solomon, CEO and co- founder of NYSCF. "One way we work towards this goal is by developing methods and models that lift the entire field of stem cell research. This new protocol is the perfect example of the type of method that will enable researchers around the world to accelerate their work." Published in Stem Cell Reports, this microglia protocol is optimized for use in high-throughput experiments, such as drug screening and toxicity testing among other large-scale research applications, and has the benefit of allowing such experiments to be carried out on multiple patient samples. The scientists determined that the protocol is robust and reproducible, generating microglia from sixteen induced pluripotent stem (iPS) cell lines, stem cells that are created from individual patients. Microglia from humans have long been a desired research model, but are difficult to obtain for laboratory experiments. The NYSCF protocol provides a new source of human microglia cells, which can be generated from disease patient samples and will complement studies in mouse models to better understand the role of microglia in health and disease. Microglia generated by the NYSCF protocol will thus provide a critical tool to investigate microglia dysfunction in central nervous system disorders and advance complex disease modeling in a dish. NYSCF scientist Dr. Panos Douvaras is first author on the paper and NYSCF scientists Dr. Scott Noggle and Dr. Valentina Fossati are co-senior authors. These NYSCF scientists worked in collaboration with colleagues from the NYSCF Research Institute and others at the Icahn School of Medicine at Mount Sinai with support from National Institute on Aging (NIA). The NIA funding was a part of the U01AG046170 consortium grant from the NIH/NIA through the Accelerating Medicines Partnership in Alzheimer's Disease. This work was also supported by the Oak Foundation and the Conrad N. Hilton Foundation. The New York Stem Cell Foundation (NYSCF) Research Institute is an independent organization accelerating cures and better treatments for patients through stem cell research. The NYSCF global community includes over 140 researchers at leading institutions worldwide, including the NYSCF - Druckenmiller Fellows, the NYSCF - Robertson Investigators, the NYSCF - Robertson Stem Cell Prize Recipients, and NYSCF Research Institute scientists and engineers. The NYSCF Research Institute is an acknowledged world leader in stem cell research and in developing pioneering stem cell technologies, including the NYSCF Global Stem Cell ArrayTM and in manufacturing stem cells for scientists around the globe. NYSCF focuses on translational research in a model designed to overcome the barriers that slow discovery and replace silos with collaboration. For more information, visit http://www. .


News Article | May 19, 2017
Site: www.biosciencetechnology.com

Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a robust, efficient method for deriving microglia, the immune cells of the brain, from human stem cells. Microglia are increasingly implicated in neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis, among many others. However, research into the role of human microglia in these disorders has long been hampered by the inability to obtain them from the human nervous system. This new protocol now enables scientists around the world to generate this critical cell type from individual patients and improve our understanding of the role of microglia neurological malfunction. "NYSCF's mission is to bring cures to patients faster," said Susan L. Solomon, CEO and co- founder of NYSCF. "One way we work towards this goal is by developing methods and models that lift the entire field of stem cell research. This new protocol is the perfect example of the type of method that will enable researchers around the world to accelerate their work." Published in Stem Cell Reports, this microglia protocol is optimized for use in high-throughput experiments, such as drug screening and toxicity testing among other large-scale research applications, and has the benefit of allowing such experiments to be carried out on multiple patient samples. The scientists determined that the protocol is robust and reproducible, generating microglia from sixteen induced pluripotent stem (iPS) cell lines, stem cells that are created from individual patients. Microglia from humans have long been a desired research model, but are difficult to obtain for laboratory experiments. The NYSCF protocol provides a new source of human microglia cells, which can be generated from disease patient samples and will complement studies in mouse models to better understand the role of microglia in health and disease. Microglia generated by the NYSCF protocol will thus provide a critical tool to investigate microglia dysfunction in central nervous system disorders and advance complex disease modeling in a dish.


News Article | April 18, 2017
Site: www.biosciencetechnology.com

MIT researchers have developed a way to make extremely high-resolution images of tissue samples, at a fraction of the cost of other techniques that offer similar resolution. The new technique relies on expanding tissue before imaging it with a conventional light microscope. Two years ago, the MIT team showed that it was possible to expand tissue volumes 100-fold, resulting in an image resolution of about 60 nanometers. Now, the researchers have shown that expanding the tissue a second time before imaging can boost the resolution to about 25 nanometers. This level of resolution allows scientists to see, for example, the proteins that cluster together in complex patterns at brain synapses, helping neurons to communicate with each other. It could also help researchers to map neural circuits, says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT. “We want to be able to trace the wiring of complete brain circuits,” said Boyden, the study’s senior author. “If you could reconstruct a complete brain circuit, maybe you could make a computational model of how it generates complex phenomena like decisions and emotions. Since you can map out the biomolecules that generate electrical pulses within cells and that exchange chemicals between cells, you could potentially model the dynamics of the brain.” This approach could also be used to image other phenomena such as the interactions between cancer cells and immune cells, to detect pathogens without expensive equipment, and to map the cell types of the body. Former MIT postdoc Jae-Byum Chang is the first author of the paper, which appears in the April 17 issue of Nature Methods. To expand tissue samples, the researchers embed them in a dense, evenly generated gel made of polyacrylate, a very absorbent material that’s also used in diapers. Before the gel is formed, the researchers label the cell proteins they want to image, using antibodies that bind to specific targets. These antibodies bear “barcodes” made of DNA, which in turn are attached to cross-linking molecules that bind to the polymers that make up the expandable gel. The researchers then break down the proteins that normally hold the tissue together, allowing the DNA barcodes to expand away from each other as the gel swells. These enlarged samples can then be labeled with fluorescent probes that bind the DNA barcodes, and imaged with commercially available confocal microscopes, whose resolution is usually limited to hundreds of nanometers. Using that approach, the researchers were previously able to achieve a resolution of about 60 nanometers. However, “individual biomolecules are much smaller than that, say 5 nanometers or even smaller,” Boyden said. “The original versions of expansion microscopy were useful for many scientific questions but couldn’t equal the performance of the highest-resolution imaging methods such as electron microscopy.” In their original expansion microscopy study, the researchers found that they could expand the tissue more than 100-fold in volume by reducing the number of cross-linking molecules that hold the polymer in an orderly pattern. However, this made the tissue unstable. “If you reduce the cross-linker density, the polymers no longer retain their organization during the expansion process,” said Boyden, who is a member of MIT’s Media Lab and McGovern Institute for Brain Research. “You lose the information.” Instead, in their latest study, the researchers modified their technique so that after the first tissue expansion, they can create a new gel that swells the tissue a second time — an approach they call “iterative expansion.” Using iterative expansion, the researchers were able to image tissues with a resolution of about 25 nanometers, which is similar to that achieved by high-resolution techniques such as stochastic optical reconstruction microscopy (STORM). However, expansion microscopy is much cheaper and simpler to perform because no specialized equipment or chemicals are required, Boyden says. The method is also much faster and thus compatible with large-scale, 3-D imaging. The resolution of expansion microscopy does not yet match that of scanning electron microscopy (about 5 nanometers) or transmission electron microscopy (about 1 nanometer). However, electron microscopes are very expensive and not widely available, and with those microscopes, it is difficult for researchers to label specific proteins. In the Nature Methods paper, the MIT team used iterative expansion to image synapses — the connections between neurons that allow them to communicate with each other. In their original expansion microscopy study, the researchers were able to image scaffolding proteins, which help to organize the hundreds of other proteins found in synapses. With the new, enhanced resolution, the researchers were also able to see finer-scale structures, such as the location of neurotransmitter receptors located on the surfaces of the “postsynaptic” cells on the receiving side of the synapse. “My hope is that we can, in the coming years, really start to map out the organization of these scaffolding and signaling proteins at the synapse,” Boyden said. Combining expansion microscopy with a new tool called temporal multiplexing should help to achieve that, he believes. Currently, only a limited number of colored probes can be used to image different molecules in a tissue sample. With temporal multiplexing, researchers can label one molecule with a fluorescent probe, take an image, and then wash the probe away. This can then be repeated many times, each time using the same colors to label different molecules. “By combining iterative expansion with temporal multiplexing, we could in principle have essentially infinite-color, nanoscale-resolution imaging over large 3-D volumes,” Boyden said. “Things are getting really exciting now that these different technologies may soon connect with each other.” The researchers also hope to achieve a third round of expansion, which they believe could, in principle, enable resolution of about 5 nanometers. However, right now the resolution is limited by the size of the antibodies used to label molecules in the cell. These antibodies are about 10 to 20 nanometers long, so to get resolution below that, researchers would need to create smaller tags or expand the proteins away from each other first and then deliver the antibodies after expansion. This study was funded by the National Institutes of Health Director’s Pioneer Award, the New York Stem Cell Foundation Robertson Award, the HHMI-Simons Faculty Scholars Award, and the Open Philanthropy Project.


News Article | February 23, 2017
Site: www.eurekalert.org

SALT LAKE CITY - Most kids say they love their mom and dad equally, but there are times when even the best prefers one parent over the other. The same can be said for how the body's cells treat our DNA instructions. It has long been thought that each copy - one inherited from mom and one from dad - is treated the same. A new study from scientists at the University of Utah School of Medicine shows that it is not uncommon for cells in the brain to preferentially activate one copy over the other. The finding breaks basic tenants of classic genetics and suggests new ways in which genetic mutations might cause brain disorders. In at least one region of the newborn mouse brain, the new research shows, inequality seems to be the norm. About 85 percent of genes in the dorsal raphe nucleus, known for secreting the mood-controlling chemical serotonin, differentially activate their maternal and paternal gene copies. Ten days later in the juvenile brain, the landscape shifts, with both copies being activated equally for all but 10 percent of genes. More than an oddity of the brain, the disparity also takes place at other sites in the body, including liver and muscle. It also occurs in humans. "We usually think of traits in terms of a whole person, or animal. We're finding that when we look at the level of cells, genetics is much more complicated than we thought," says Christopher Gregg, Ph.D., assistant professor of neurobiology and anatomy and senior author of the study which publishes online in Neuron on Feb. 23. "This new picture may help us understand brain disorders," he continues. Among genes regulated in this unorthodox way are risk factors for mental illness. In humans, a gene called DEAF1, implicated in autism and intellectual disability, shows preferential expression of one gene copy in multiple regions of the brain. A more comprehensive survey in primates, which acts as a proxy for humans, indicates the same is true for many other genes including some linked to Huntington's Disease, schizophrenia, attention deficit disorder, and bipoloar disorder. What the genetic imbalance could mean for our health remains to be determined, but preliminary results suggest that it could shape vulnerabilities to disease, explains Gregg. Normally, having two copies of a gene acts as a protective buffer in case one is defective. Activating a gene copy that is mutated and silencing the healthy copy - even temporarily - could be disruptive enough to cause trouble in specific cells. Supporting the idea, Gregg's lab found that some brain cells in transgenic mice preferentially activate mutated gene copies over healthy ones. "It has generally been assumed that there is correlation between both copies of a gene," says Elliott Ferris, a computer scientist who co-led the study with graduate student Wei-Chao Huang. Instead, they found something unexpected. "We developed novel methods for mining big data, and discovered something new," Huang explains. The investigators screened thousands of genes in their study, quantifying the relative levels of activation for each maternal and paternal gene copy and discovered that expression of the two is different for many genes. Surprised by what they saw, they developed statistical methods to rigorously test their validity and determined that they were not due to technical artifacts, nor genetic noise. Following up on their findings, they examined a subset of genes more closely, directly visualized imbalances between gene copies at the cellular level in the mouse and human brain. Results from Gregg and colleagues build on previous research, expanding on scenarios in which genes play favorites. Imprinted genes and X-linked genes are specific gene categories that differentially activate their maternal and paternal gene copies. Studies in cultured cells had also determined that some genes vary which copy they express. The results from this study, however, suggests that silencing one gene copy may be a way in which cells fine tune their genetic program at specific times during the lifecycle of the animal, or in discrete places. "Our new findings reveal a new landscape of diverse effects that shape the expression of maternal and paternal gene copies in the brain according to age, brain region, and tissue type," explains Gregg. "The implication is a new view of genetics, one that starts up close." The research was supported by the National Institutes of Health, Simons Foundation, University of Utah, and New York Stem Cell Foundation. In addition to Gregg, Huang, and Ferris, co-authors are Tong Cheng, Cornelia Stacher Horndli, Kelly Gleason, Carol Tamminga, Kenneth Boucher, and Jan Christian from the University of Utah, and Janice Wagner from Wake Forest School of Medicine. The study publishes in Neuron as "Diverse Non-Genetic Allele Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain".


News Article | February 23, 2017
Site: www.eurekalert.org

For over a century, scientists have thought that most of our cells express genes from both parents' chromosomes relatively equally throughout life. But the biology is more nuanced, say scientists who invented a screen to measure the activity of specific genes from both parents. In Neuron on February 23, the researchers report that in rodent, monkey, and human brains, it's not unusual for individual neurons or specific types of neurons to silence genes from one parent or the other. Surprisingly, the differential activation of maternal and paternal gene copies was observed most often in the developing brain, impacting about 85% of genes. Gradually, as the brain matures, neurons increasingly express both parents' genes equally. However, for at least 10% of genes, maternal and paternal copies continue to be differentially expressed in the adult brain, revealing that this imbalance exists throughout an organism's lifetime for many genes in the brain. "This story has its roots in understanding why we reproduce sexually--normally, having two copies of a gene acts as a protect buffer in case one is defective," says senior author Christopher Gregg (@GreggNeuroLab), a neurobiologist at the University of Utah School of Medicine and a New York Stem Cell Foundation Robertson Investigator. "Our findings suggest that periods when the healthy gene copy is turned off could be critical windows during which cells are particularly vulnerable to a mutation in the other copy." Often mutations causing mental illness are heterozygous, meaning that they impact just one gene copy, and the Gregg lab is now exploring whether the effects they uncovered could explain why the same gene can be associated with a wide range of mental illnesses, from autism to schizophrenia, and why different people experience variation in the severity of their symptoms or risk for disease. The study demonstrates that it is possible for some cells in the brain to predominately express a mutant copy of a gene while others don't. Scientists have known for decades that some specific classes of genes differentially activate their maternal and paternal copies in the brain; however, the study from Gregg's lab uncovered a new and vast landscape of effects in the brain that cause differences in the activation of maternal and paternal gene copies according to age, cell type, brain region, and tissue. The study also raises the possibility of yet undiscovered mechanisms for how cells decide which parent's genes to shut off. Currently, it's known that children can inherit epigenetic imprints on their genome from parents that communicate whether a gene should be expressed, and for females, each cell inactivates one X chromosome. Finding the mechanisms that cause the effects described in the Gregg lab's new study could lead to new therapeutic approaches that work by activating silent healthy gene copies in the brain. "The screens revealed a new landscape of effects on maternal and paternal gene copies in the brain that were not due to imprinting and not due to X inactivation but took on all kinds of different forms," Gregg says. "Some effects are age specific, some are stable after birth, some impact most brain cells, some are more cell specific, some involved antagonistic effects where the maternal gene would go up and the paternal gene would go down, while others took on a different pattern." Gregg and his team at the University of Utah, including co-first authors Wei-Chao Huang, a graduate student, and Elliott Ferris, a bioinformatician, are now focused on understanding how differences in parental gene expression shape brain functions and disease risk. And while they are specifically looking at brain cells and mental illness, the screen they developed, now available to the scientific community, could provide insights across many cell types. This work has been supported by the National Institutes of Health, a Simons Foundation Autism Research Initiative Explorer Award, a University of Utah Seed Grant, and a New York Stem Cell Foundation Robertson-Neuroscience Award. Neuron, Huang and Ferris et al.: "Diverse Non-Genetic Allele Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain" http://www.cell.com/neuron/fulltext/S0896-6273(17)30057-0 Neuron (@NeuroCellPress), published by Cell Press, is a bimonthly journal that has established itself as one of the most influential and relied upon journals in the field of neuroscience and one of the premier intellectual forums of the neuroscience community. It publishes interdisciplinary articles that integrate biophysical, cellular, developmental, and molecular approaches with a systems approach to sensory, motor, and higher-order cognitive functions. Visit: http://www. . To receive Cell Press media alerts, contact press@cell.com.


Patent
Columbia University and New York Stem Cell Foundation | Date: 2012-10-10

The present invention is based on the discovery that certain small molecules can relieve ER stress, leading to increased insulin production in beta cells and improved insulin secretion. Methods of treating a disease or disorder in a subject, wherein the disease or disorder is characterized by intracellular endoplasmic reticulum (ER) stress, by administering to the subject, an effective amount of a compound that is an ER stress reliever, are provided herein.


Patent
New York Stem Cell Foundation | Date: 2013-12-05

The present invention provides modified oocytes having a nuclear genome derived from a first oocyte and cytoplasm derived from a second oocyte from a different subject, and methods for making and using such modified oocytes. The methods and compositions of the present invention can be useful in a variety of settings including, but not limited to, in in vitro fertilization (IVF) procedures.


Patent
New York Stem Cell Foundation | Date: 2012-11-30

The invention provides an automated system for producing induced pluripotent stem cells (iPSCs) from adult somatic cells. Further, the system is used for producing differentiated adult cells from stem cells. The invention system is useful for isolating somatic cells from tissue samples, producing iPSC lines from adult differentiated cells by reprogramming such cells, identifying the pluripotent reprogrammed adult cells among other cells, and expanding and screening the identified reprogrammed cells.

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