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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Perspective: The promise of multi-cellular engineered living systems.
Roger D. Kamm,Rashid Bashir,Natasha Arora,Roy D. Dar,Martha U. Gillette,Linda G. Griffith,Melissa L. Kemp,Kathy Kinlaw,Michael Levin,Adam C. Martin,Todd C. McDevitt,Robert M. Nerem,Mark J. Powers,Taher A. Saif,James Sharpe,Shuichi Takayama,Shoji Takeuchi,Ron Weiss,Kaiming Ye,Hannah G. Yevick,Muhammad H. Zaman +20 more
TL;DR: The state of the emerging field of “multi-cellular engineered living systems,” which are composed of interacting cell populations, is summarized, focusing on current and potential applications, as well as barriers to future advances.
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Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights Into Altered Brain Maturation.
TL;DR: Key time windows of development during which the immature brain is vulnerable to injury are described and special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function.
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Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes
Paola Conforti,Dario Besusso,Vittoria Dickinson Bocchi,Andrea Faedo,Elisabetta Cesana,Grazisa Rossetti,Valeria Ranzani,Clive N. Svendsen,Leslie M. Thompson,Mauro Toselli,Gerardo Biella,Massimiliano Pagani,Elena Cattaneo +12 more
TL;DR: It is reported that huntingtin mutation affects specific aspects of human neurodevelopment at the level of neuronal progenitor specification and its early commitment, leading to an abnormal cell organization and acquisition of mature neuronal identities in cerebral organoids.
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Organoid culture systems to study host-pathogen interactions.
Devanjali Dutta,Hans Clevers +1 more
TL;DR: The most recent and striking studies on host–microbe interactions in organoid cultures are discussed, highlighting various methods which can be used for developing microbe-organoid co-culture systems.
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Scaffolds for 3D in vitro culture of neural lineage cells.
TL;DR: A state of the art update on three-dimensional culture systems for in vitro development of neural tissue, employing a wide range of scaffold types including hydrogels, solid porous polymers, fibrous materials and decellularised tissues as well as microfluidic devices and lab-on-a-chip systems.
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