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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Synthetic alternatives to Matrigel.
TL;DR: The limitations of Matrigel are discussed and synthetic alternatives for stem-cell culture, regenerative medicine and organoid assembly are highlighted and xenogenic-free, chemically defined, highly tunable and reproducible alternatives are highlighted.
Journal ArticleDOI
Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue
Hideya Sakaguchi,Taisuke Kadoshima,Mika Soen,Nobuhiro Narii,Yoshihito Ishida,Masatoshi Ohgushi,Jun Takahashi,Mototsugu Eiraku,Yoshiki Sasai +8 more
TL;DR: An in vitro model that recapitulates human hippocampus development is developed, allowing the generation of functional hippocampal granule- and pyramidal-like neurons.
Journal ArticleDOI
Self-Organizing 3D Human Neural Tissue Derived from Induced Pluripotent Stem Cells Recapitulate Alzheimer’s Disease Phenotypes
Waseem K. Raja,Alison E. Mungenast,Yuan-Ta Lin,Tak Ko,Fatema Abdurrob,Jinsoo Seo,Li-Huei Tsai +6 more
TL;DR: It is found that treatment of patient-derived organoids with β- and γ-secretase inhibitors significantly reduces amyloid and tau pathology and the potential of this model system to greatly increase the translatability of pre-clinical drug discovery in AD is shown.
Journal ArticleDOI
Induced Pluripotent Stem Cells Meet Genome Editing
Dirk Hockemeyer,Rudolf Jaenisch +1 more
TL;DR: How two such experiments-the generation of human induced pluripotent stem cells (iPSCs) and the development of CRISPR/Cas9 technology-have fundamentally reshaped the approach to biomedical research, stem cell biology, and human genetics is reviewed.
Journal ArticleDOI
Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.
Alex A. Pollen,Aparna Bhaduri,Madeline G. Andrews,Tomasz J. Nowakowski,Olivia S. Meyerson,Mohammed A. Mostajo-Radji,Elizabeth Di Lullo,Beatriz Alvarado,Melanie Bedolli,Max L. Dougherty,Ian T. Fiddes,Zev N. Kronenberg,Joe Shuga,Anne A. Leyrat,Jay A. A. West,Marina Bershteyn,Craig B. Lowe,Bryan J Pavlovic,Sofie R. Salama,David Haussler,David Haussler,Evan E. Eichler,Arnold R. Kriegstein +22 more
TL;DR: This work leveraged recent innovations that permit generating pluripotent stem cell-derived cerebral organoids from chimpanzee to identify human-specific features of cortical development and identifies 261 differentially expressed genes in human compared to both chimpanzee organoids and macaque cortex.
References
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