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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3D in vitro modeling of the central nervous system.
TL;DR: Critical challenges remain including biomaterials capable of matching the mechanical properties and extracellular matrix composition of neural tissues, compartmentalized scaffolds that support heterogeneous tissue architectures reflective of brain organization and structure, and robust functional assays for in vitro tissue validation.
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Using brain organoids to understand Zika virus-induced microcephaly
TL;DR: The advantages of brain organoids over other model systems to study development and recent advances in understanding ZIKV pathophysiology and its underlying pathogenesis mechanisms are highlighted.
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Monoamine neurotransmitter disorders—clinical advances and future perspectives
TL;DR: The clinical features, diagnosis and management of monoamine neurotransmitter disorders are discussed, and novel concepts, the latest advances in research and future prospects for therapy are considered.
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3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels
TL;DR: In this paper, the authors developed a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization.
Journal ArticleDOI
A Quantitative Framework to Evaluate Modeling of Cortical Development by Neural Stem Cells
Jason L. Stein,Luis de la Torre-Ubieta,Yuan Tian,Neelroop N. Parikshak,Israel Hernandez,Maria C. Marchetto,Dylan K. Baker,Daning Lu,Cassidy R. Hinman,Jennifer K. Lowe,Eric M. Wexler,Alysson R. Muotri,Fred H. Gage,Kenneth S. Kosik,Daniel H. Geschwind +14 more
TL;DR: Significant differences between in vitro models are observed, including hiPSC-derived neural progenitors from multiple laboratories, and a machine learning approach called CoNTExT is developed and validated that identifies the developmental maturity and regional identity of in-vItro models.
References
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