Axolotls have the ability to regenerate multiple organs, including their brains, throughout the course of their lives. This makes them an ideal model to study brain regeneration, particularly whether neuronal diversity, intricate tissue architecture and neuron connectivity can be regenerated.
NYSCF - Robertson Stem Cell Investigator Dr. Paola Arlotta, Harvard University, demonstrated that diverse, electrophysiologically functional neurons can be regenerated in axolotls after mechanical injury in her latest paper published in Elife. Research on brain repair in regenerative species helps pave the way for the eventual development of successful cell replacement strategies and repairs in the central nervous system of people.
The 3D structure of a cell’s genetic code, or genome, helps guide genetic expression. Though it is known that this structure is rearranged in somatic cells during reprogramming into induced pluripotent stem cells, this process is poorly understood.
NYSCF – Robertson Stem Cell Investigator Dr. Jennifer Phillips-Cremins, University of Pennsylvania, investigates this phenomenon in her work recently published in Cell Stem Cell. In an effort to shed light on how the cellular genome structure is reconfigured during reprogramming, Dr. Phillips-Cremins and her team compared epigenetic marks and gene expression between different types of cells, showing that induced pluripotent stem cell genomes can have mistakes in their 3D folding linked to inaccurately reprogrammed gene expression.
This research has implications on how to develop the best possible cells for future regenerative medicine applications.
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.