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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A Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found In Vivo
Christopher G. Hubert,Maricruz Rivera,Lisa C. Spangler,Qiulian Wu,Stephen C. Mack,Briana C. Prager,Marta Couce,Roger E. McLendon,Andrew E. Sloan,Jeremy N. Rich +9 more
TL;DR: A three-dimensional culture system that supports the long-term growth and expansion of tumor organoids derived directly from glioblastoma specimens, including patient-derived primary cultures, xenografts, genetically engineered glioma models, or patient samples is described.
Journal ArticleDOI
Organoids: A historical perspective of thinking in three dimensions.
Marina Simian,Mina J. Bissell +1 more
TL;DR: In this perspective, Simian and Bissell discuss the evolution of the 3D culture and organoid research field up to now as well as its future directions.
Journal ArticleDOI
Pluripotent stem cells in regenerative medicine: challenges and recent progress
Viviane Tabar,Lorenz Studer +1 more
TL;DR: Recent progress in directed differentiation, some of the new technologies that have facilitated the success of hPSC therapies and the remaining hurdles on the road towards developing hPSc-based cell therapies are discussed.
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Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development.
Cleber A. Trujillo,Richard Gao,Priscilla D. Negraes,Jing Gu,Justin Buchanan,Sebastian Preissl,Allen Wang,Wei Wu,Gabriel G. Haddad,Isaac A. Chaim,Alain Domissy,Matthieu Vandenberghe,Anna Devor,Gene W. Yeo,Bradley Voytek,Alysson R. Muotri +15 more
TL;DR: Human cortical organoids that dynamically change cellular populations during maturation and exhibited consistent increases in electrical activity over the span of several months show that the development of structured network activity in a human neocortex model may follow stable genetic programming.
Journal ArticleDOI
Modeling mouse and human development using organoid cultures.
Meritxell Huch,Bon-Kyoung Koo +1 more
TL;DR: Recent advances in the generation of pluripotent stem cell- and AdSC-derived organoids are discussed, highlighting their potential for enhancing the understanding of human development and how this new culture system allows disease modeling and gene repair for a personalized regenerative medicine approach.
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