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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Biofabrication of neural microphysiological systems using magnetic spheroid bioprinting.
Devon A. Bowser,Michael J. Moore +1 more
TL;DR: This work serves as a proof-of-concept for merging the two approaches to create a neural microphysiological system that overcomes their individual limitations and provides the first steps towards developing a simple approach for integrating spheroid, hydrogel culture, and bioprinting as an alternative to more specialized and expensive processes.
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Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids.
Ai Tian,Julien Muffat,Yun Li +2 more
TL;DR: This work evaluates the recent progress in brain organoid technology, and discusses the experimental considerations for its utilization, and considers integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems.
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Models for discovery of targeted therapy in genetic epileptic encephalopathies
TL;DR: This review addresses efforts to advance and use experimental models to identify specific molecular and cellular targets for the development of novel therapies in epileptic encephalopathies and focuses on ion channels as the best‐studied group of epilepsy genes.
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Modeling the Human Body on Microfluidic Chips
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Journal ArticleDOI
Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis
Alejandro López-Tobón,Alejandro López-Tobón,Carlo Emanuele Villa,Cristina Cheroni,Cristina Cheroni,Sebastiano Trattaro,Sebastiano Trattaro,Nicolò Caporale,Nicolò Caporale,Paola Conforti,Raffaele Iennaco,Maria Lachgar,Marco Tullio Rigoli,Berta Marcó de la Cruz,Pietro Lo Riso,Erika Tenderini,Flavia Troglio,Marco De Simone,Isabel Liste-Noya,Giuseppe Macino,Massimiliano Pagani,Elena Cattaneo,Giuseppe Testa,Giuseppe Testa +23 more
TL;DR: The dissection of the GSK3-dependent transcriptional network in human corticogenesis underscores the robustness of the programs determining neuronal identity independent of tissue architecture.
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