NYSCF Principal Investigator Dr. Valentina Fossati and a team of NYSCF Research Institute scientists continued to unravel the mysteries of multiple sclerosis with her latest paper investigating the precise cues leading to proper development of oligodendrocytes, the brain cells affected by the disease.
Current knowledge on the processes of oligodendrocyte differentiation and maturation comes from extensive research using rodent models. This research, published in the International Journal of Molecular Sciences, used human induced pluripotent stem cells, stem cells made from adult skin or blood samples, to show that the process of oligodendrocyte development in humans is similar to that in rodent models.
A thorough understanding of the processes leading to the generation of myelinating oligodendrocytes is important not only for multiple sclerosis, but also for a vast number of other neurological and psychiatric disorders.
NYSCF – Robertson Stem Cell Investigator Dr. Kristen Brennand, Icahn School of Medicine at Mount Sinai, used advanced stem cell technology to support the hypothesis that a certain subset of schizophrenia patients are genetically set on a path to develop the disease before birth.
Published in Cell Reports, the researchers took skin samples from patients with schizophrenia and reprogrammed these cells into stem cells, then turned these stem cells into cells resembling fetal schizophrenic brain cells. The researchers then demonstrated that these brain cells under-expressed an important group of molecules, called microRNA-9s, that is important for the growth and maturation of brain cells in the fetal brain. This under-expression means that neural pathways may never develop properly.
Schizophrenic patients rarely display symptoms before early adulthood, making the cellular origins of the disease difficult to dissect. This research suggests that a subset of schizophrenia patients with extreme microRNA-9s under-expression were already at risk for developing schizophrenia during prenatal development before birth.
When people recall memories or make decisions neurons are activated and signals are shuttled through a sequence of these brain cells. NYSCF – Robertson Neuroscience Investigator Christopher Harvey, Harvard Medical School, co-authored a paper published in Neuron showing that these neural sequences may arise out of networks of neurons that appear unstructured. The research uses cellular level images of these neuronal networks which reveals that the information transferred through the neurons does not move in one, forward direction, but rather the network is “recurrent.” Dr. Harvey’s important contributions to understanding the brain help researchers make sense of the way information is transferred through networks of cells in the brain, and helps illuminate how humans think.
The incredible advances in technology over the past two decades have given scientists the power to map the human brain. Researchers now know where in the brain different emotions and reactions are processed and many of the different connections between different brain regions.
NYSCF – Robertson Neuroscience Investigator Kay Tye, MIT, parses brain signals and makes sense of how different neurons interact. In her most recent research published in Neuron, Dr. Tye studies how memories with positive and negative connotations are routed through different neuronal pathways. Her results show that there are special populations of neurons that tend to excite more for positive-associations and other neurons that tend to excite more for negative-associations. This work begins to provide necessary information to explain how humans might assign emotions to events — a critical component of some mental illnesses wherein emotions and events mismatch.
NYSCF spoke with Dr. Valentina Fossati who leads NYSCF’s multiple sclerosis research on the future of MS treatments and how stem cells have changed the field of MS research.
NYSCF – Robertson Investigator Dr. Feng Zhang received the 2016 Canada Gairdner Award for his work developing revolutionary tools to edit DNA in establishing and enhancing the CRISPR-Cas technology. The prestigious Canada Gairdner Awards recognize outstanding international biomedical research. This year’s awards lauded a group of scientists including Dr. Zhang, Broad Institute of Harvard and MIT, for their research developing the CRISPR-Cas tool for quick and efficient genome editing that has changed how and what scientists can do around the world.
Normal human cells contain two copies of each gene – one inherited from a mother, and one from a father. An international collaboration of scientists including NYSCF Senior Research Fellow and NYSCF – Robertson Investigator Dr. Dieter Egli created human stem cells, cells that can mature into any type of cell in the body, with only one copy of each gene. These cells are known as ‘haploid’ cells since they maintain only one set of the genome, half, as opposed to the normal two sets. The research, published in Nature, represents a landmark in research techniques and biotechnology. These haploid stem cells mark the first time scientists created cells that can grow and divide infinitely with only one copy of the human genome.
For scientists, this unprecedented achievement will accelerate the pace of biomedical research and potential cell-based therapies. Typically, two copies of a gene means that cells have two chances to get it right, make a protein that functions correctly. However, on rare occasions both copies of a gene are faulty which can lead to painful lifelong conditions. For example, individuals with sickle cell disease inherit two damaged copies of a protein in blood cells; likewise, those suffering from cystic fibrosis contain mutations in both of their genes for a protein that transports small molecules across cell membranes. Scientists making sense of gene functions and different diseases currently must manipulate genomes to try to remove both copies of their gene of interest. With haploid cells, researchers can readily cut out, engineer, or tweak the single gene copy, an invaluable tool for speeding up the process of discovery giving researchers the power to study more complex diseases like diabetes and Alzheimer’s which may involve multiple faulty genes.
Excitingly this study by researchers at The Hebrew University of Jerusalem, Columbia University Medical Center, and NYSCF establishes that despite only having one copy of the genome these cells can be coaxed into becoming cells of any type of the three germ layers in embryos. This means that not only can scientists maintain cells with half the normal amount of DNA in an undifferentiated, stem cell state, but that researchers can also transform these cells into any cell type of interest and readily manipulate the single-copy genome. Creating cell-based treatments, understanding disease and discovering what it means to be human is even easier with this NYSCF-enabled breakthrough.
(Image: A haploid cell with 23 chromosomes (left), and a diploid cell with 46 chromosomes (right). Credit: Gloryn Chia/Columbia University Medical Center)
NYSCF-Robertson Neuroscience Investigator Michael A. Long, NYU, cooled areas of the brain associated with speech to see the effects on patients. Previously, neuroscientists have relied on electrically stimulating brain regions to understand their functions and ensure that no critical parts of the brain are excised during surgeries to remove tumors and other operations. During these procedures patients remain awake so that doctors can assess the importance of different brain areas. However, stimulating the brain with electricity can trigger epileptic seizures. Dr. Long and his group developed a method to cool brain areas, rather than use electricity, to understand the critical nature of different brain areas and their connection to speech. The resulting study, published in Neuron, examines areas in the brain linked to speech using this method to disrupt speaking in patients undergoing surgical operations. The research shows that areas of the brain that control speech are positioned closely together, highly localized. Dr. Long also elucidates the function of brain structures, specifically identifying structures in the brain that control muscle movement of the tongue and lips and parts that control the speed of these muscle movements. Dr. Long hopes that this and downstream research will help the medical community develop more affective therapies to help patients who have lost the ability to speak.