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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Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
Susanne C. van den Brink,Peter Baillie-Johnson,Tina Balayo,Anna-Katerina Hadjantonakis,Sonja Nowotschin,David A. Turner,Alfonso Martinez Arias +6 more
TL;DR: It is reported that small aggregates of mESCs self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation.
Journal ArticleDOI
Cerebral organoids at the air–liquid interface generate diverse nerve tracts with functional output
Stefano L. Giandomenico,Susanna B. Mierau,George M. Gibbons,Léa M. D. Wenger,Laura Masullo,Timothy Sit,Magdalena Sutcliffe,Jérôme Boulanger,Marco Tripodi,Emmanuel Derivery,Ole Paulsen,Andras Lakatos,Madeline A. Lancaster +12 more
TL;DR: A modified brain-organoid culture is adapted to cerebral organoids, leading to improved neuronal survival and axon outgrowth, revealing a remarkable self-organization of corticofugal and callosal tracts with a functional output.
Journal ArticleDOI
Cell stress in cortical organoids impairs molecular subtype specification
Aparna Bhaduri,Madeline G. Andrews,Walter R Mancia Leon,Diane Jung,David Shin,Denise Allen,Dana Jung,Galina Schmunk,Maximilian Haeussler,Jahan Salma,Alex A. Pollen,Tomasz J. Nowakowski,Arnold R. Kriegstein +12 more
TL;DR: Single-cell RNA sequencing clarifies the development and specification of neurons in the human cortex and shows that cell stress impairs this process in cortical organoids.
Journal ArticleDOI
Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids
Leonardo Beccari,Naomi Moris,Mehmet Girgin,David A. Turner,Peter Baillie-Johnson,Anne-Catherine Cossy,Matthias P. Lutolf,Denis Duboule,Denis Duboule,Alfonso Martinez Arias +9 more
TL;DR: It is shown that small aggregates of mouse embryonic stem cells, when stimulated to undergo gastrulation-like events and elongation in vitro, can organize a post-occipital pattern of neural, mesodermal and endodermal derivatives that mimic embryonic spatial and temporal gene expression.
Journal ArticleDOI
Gyrification from constrained cortical expansion
TL;DR: In this article, the authors show that the brain gyrification can arise as a nonlinear consequence of a simple mechanical instability driven by tangential expansion of the gray matter constrained by the white matter.
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