Brain Organoids Special Issue April 12, 2018 | |
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We’ve noticed a new trend when curating Neural Cell News and ESC & iPSC News – brain organoids are everywhere! As scientists are increasingly incorporating these revolutionary ‘mini-brains’ into their research, the news media has caught on. Our job is to keep you informed on the top scientific research and news in your field. So, we’ve collected some of our favorite news stories and seminal publications to share with you in this special “Brain Organoids” issue. We hope you enjoy them as much as we have. If you like this special issue, let us know by replying to this email. Maybe we’ll do more! Yours in science communication, | |
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SELECTED NEWS STORIES“In a white lab coat and blue latex gloves, Neda Vishlaghi peers through a light microscope at six milky-white blobs. Each is about the size of a couscous grain, bathed in the pale orange broth of a petri dish. With tweezers in one hand and surgical scissors in the other, she deftly snips one tiny clump in half.” [Science News] Article Why Two Brains Are Better than One “Last week, I was told my other brain is fully grown. It doesn’t look like much. A blob of pale flesh about the size of a small pea, it floats in a bath of blood-red nutrient. It would fit into the cranium of a foetus barely a month old.” [The Guardian] Article Lab-Grown ‘Minibrains’ Are Revealing What Makes Humans Special “Ever since Alex Pollen was a boy talking with his neuroscientist father, he wanted to know how evolution made the human brain so special. Our brains are bigger, relative to body size, than other animals’, but it’s not just size that matters.” [ScienceInsider] Article Lab-Grown Mini Organs Could Speed Up Drug Discovery “The thought of lab-grown organs conjures up Frankenstein-like imagery. The reality however, is somewhat less visually dramatic, with the term ‘organoids’ used to describe tiny 3D structures of human tissue, a millimeter or so in diameter. Although, frankly, underwhelming to look at without a microscope, these tiny lumps of cells are creating a lot of excitement in the world of medical research.” [Forbes] Article One Great Way to Study Brain Diseases? ‘Mini-Brains’ Grown in Dishes “The concept of scientists growing “mini-brains in dishes” might sound like the plot of a movie. However, this is exactly what scientists are doing. In the lab, these conceptual “mini-brains” are called organoids. They’re cultivated from stem cells in an artificial environment outside the body and self-organize to form 3D structures which, in part, resemble organs within the body. Lungs, pancreas, fallopian tubes, even taste buds – you name it, an organoid can be made to resemble it.” [Massive Science Inc.] Article | |
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SELECTED PUBLICATIONS(Sorted by date)Scientists describe optimized organoid culture methods that efficiently and reliably produce cortical and basal ganglia structures similar to those in the human fetal brain in vivo. They demonstrated the utility of this organoid system for modeling the teratogenic effects of Zika virus on the developing brain and identifying more susceptibility receptors and therapeutic compounds that can mitigate its destructive actions. [Cell Rep] Full Article | Graphical Abstract Human Brain Organoids on a Chip Reveal the Physics of Folding Researchers report the appearance of surface wrinkles during the in vitro development and self-organization of human brain organoids in a microfabricated compartment that supports in situ imaging over a timescale of weeks. [Nat Phys] Abstract Guided Self-Organization and Cortical Plate Formation in Human Brain Organoids While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. The authors combined these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. [Nat Biotechnol] Abstract Cell Diversity and Network Dynamics in Photosensitive Human Brain Organoids Investigators found that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli. [Nature] Abstract Assembly of Functionally Integrated Human Forebrain Spheroids Researchers generated 3D spheroids from human pluripotent stem cells that resemble either the dorsal or ventral forebrain and contain cortical glutamatergic or GABAergic neurons. These subdomain-specific forebrain spheroids could be assembled in vitro to recapitulate the saltatory migration of interneurons observed in the fetal forebrain. [Nature] Abstract Scientists showed that two recently isolated strains of Zika virus, an American strain from an infected fetal brain and a closely-related Asian strain, productively infect human iPSC-derived brain organoids. [Cell Stem Cell] Full Article | Graphical Abstract Researchers developed a method to differentiate human PSCs into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. They detected electrically active and functionally mature midbrain dopaminergic neurons and dopamine production in their 3D midbrain-like organoids. [Cell Stem Cell] Full Article | Graphical Abstract Brain-Region-Specific Organoids Using Mini-Bioreactors for Modeling ZIKV Exposure The authors developed a miniaturized spinning bioreactor to generate forebrain-specific organoids from human iPSCs. They employed the forebrain organoid platform to model Zika virus (ZIKV) exposure. ZIKV infection lead to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly. [Cell] Full Article | Graphical Abstract FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders Investigators used 3D neural cultures derived from iPSCs to investigate neurodevelopmental alterations in individuals with severe idiopathic autism spectrum disorder (ASD). ASD-derived organoids exhibited an accelerated cell cycle and overproduction of GABAergic inhibitory neurons. Using RNA interference, they showed that overexpression of the transcription factor FOXG1 is responsible for the overproduction of GABAergic neurons. [Cell] Full Article | Graphical Abstract The Brazilian Zika Virus Strain Causes Birth Defects in Experimental Models Scientists demonstrated that Brazilian Zika virus infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infected human cortical progenitor cells, leading to an increase in cell death. They report that the infection of human brain organoids resulted in a reduction of proliferative zones and disrupted cortical layers. [Nature] Full Article Functional Cortical Neurons and Astrocytes from Human Pluripotent Stem Cells in 3D Culture Researchers present a simple and reproducible 3D culture approach for generating a laminated cerebral cortex-like structure, named human cortical spheroids (hCSs), from PSCs. hCSs contained neurons from both deep and superficial cortical layers and mapped transcriptionally to in vivo fetal development. These neurons were electrophysiologically mature, displayed spontaneous activity, were surrounded by nonreactive astrocytes and formed functional synapses. [Nat Methods] Abstract Using 3D culture of human ES cells, scientists showed new self-organizing aspects of human corticogenesis: spontaneous development of intracortical polarity, curving morphology, and complex zone separations. This culture generated species-specific progenitors, outer radial glia, which are abundantly present in the human, but not mouse, neocortex. [Proc Natl Acad Sci USA] Full Article Cerebral Organoids Model Human Brain Development and Microcephaly Cerebral organoids were shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Scientists used RNA interference and patient-specific iPSCs to model microcephaly, a disorder that has been difficult to recapitulate in mice. They demonstrated premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. [Nature] Abstract Investigators demonstrated self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient 3D aggregation culture. The generated cortical neurons were functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. [Cell Stem Cell] Full Article | |
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SELECTED REVIEWSThe Rise of Three-Dimensional Human Brain Cultures Region-specific 3D brain cultures can be derived from any individual and assembled to model complex cell-cell interactions and to generate circuits in human brain assembloids. The author discusses how this approach can be used to understand unique features of the human brain and to gain insights into neuropsychiatric disorders. [Nature] Abstract Organogenesis in a Dish: Modeling Development and Disease Using Organoid Technologies Because organoids can be grown from human stem cells and from patient-derived iPSCs, they have the potential to model human development and disease. Furthermore, they have potential for drug testing and even future organ replacement strategies. Investigators summarize this rapidly evolving field and outline the potential of organoid technology for future biomedical research. [Science] Abstract The Use of Brain Organoids to Investigate Neural Development and Disease Recent advances in stem cell technologies that enable the generation of human brain organoids from PSCs promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases. [Nat Rev Neurosci] Abstract | |
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