Cerebral organoids model human brain development and microcephaly
Madeline A. Lancaster,Magdalena Renner,Carol Anne Martin,Daniel Wenzel,Louise S. Bicknell,Matthew E. Hurles,Tessa Homfray,Josef M. Penninger,Andrew P. Jackson,Juergen A. Knoblich +9 more
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TLDR
A human pluripotent stem cell-derived three-dimensional organoid culture system that develops various discrete, although interdependent, brain regions that include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes is developed.Abstract:
The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissueread more
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Tubular human brain organoids to model microglia-mediated neuroinflammation
Zheng Ao,Hongwei Cai,Zhuhao Wu,Sunghwa Song,Hande Karahan,Byung-Wook Kim,Hui-Chen Lu,Jungsu Kim,Ken Mackie,Feng Guo +9 more
TL;DR: In this article, a tubular organoid-on-a-chip device is presented to generate better organoids and model neuro-inflammation by employing 3D printed hollow mesh scaffolds, which can be easily incorporated into multiwell-plates for reliable, scalable and reproducible generation of tubular organs.
Journal ArticleDOI
Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals
TL;DR: Extensive evidence for positive selection having acted on the majority of microcephaly loci not just in primates but also across non-primate mammals is found, suggesting that ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size in mammals.
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3D bioprinting models of neural tissues: The current state of the field and future directions.
Laura De la Vega,Christopher Lee,Ruchi Sharma,Meitham Amereh,Stephanie M. Willerth,Stephanie M. Willerth +5 more
TL;DR: How 3D hydrogels can serve as powerful tools for engineering neural tissue, especially when combined with different types of cells, is discussed, to gain a better understanding of neural tissue development and its associated disease states.
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Modelling Sporadic Alzheimer's Disease Using Induced Pluripotent Stem Cells.
TL;DR: This review compares the data obtained from fAD and sAD iPSC-derived cell lines, identifies the inconsistencies that exist in sAD models, and highlights the potential role of Aβ clearance mechanisms, a relatively under-investigated area in i PSCs, in the study of AD.
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Gene-Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres.
Sergio Modafferi,Sergio Modafferi,Xiali Zhong,Xiali Zhong,Andre Kleensang,Yohei Murata,Francesca Fagiani,Francesca Fagiani,Francesca Fagiani,David Pamies,David Pamies,Helena T. Hogberg,Vittorio Calabrese,Herbert M. Lachman,Thomas Hartung,Thomas Hartung,Lena Smirnova +16 more
TL;DR: In this article, the mechanism of gene-environment interactions and reliable bi-particle bi-connections were used to diagnose autism spectrum disorder (ASD) caused by complex genetic and environmental components.
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