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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Demethylation of induced pluripotent stem cells from type 1 diabetic patients enhances differentiation into functional pancreatic β cells.
TL;DR: In this article, the authors used induced pluripotent stem (iPS) cells derived from patients with Type 1 diabetes to generate glucose-responsive, insulin-producing cells (IPCs) via 3D culture.
Journal ArticleDOI
Using Patient-Derived Induced Pluripotent Stem Cells to Model and Treat Epilepsies.
Xixi Du,Jack M. Parent +1 more
TL;DR: The application of powerful new tools such as genome editing and multi-well, multi-electrode array recording platforms to iPSC disease modeling and therapy development for the epilepsies is discussed.
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Neurotropic Effects of SARS-CoV-2 Modeled by the Human Brain Organoids.
TL;DR: In this article, the neurotoxic effects of SARS-CoV-2 using brain organoids are summarized and comprehensively discuss how brain organoid could further improve our understanding when they are fine-tuned.
Journal ArticleDOI
Differential antiviral immunity to Japanese encephalitis virus in developing cortical organoids.
Boya Zhang,Yangzhige He,Yan-Peng Xu,Fan Mo,Ting-Wei Mi,Qing Sunny Shen,Chunfeng Li,Yali Li,Jing Liu,Yihui Wu,Guilai Chen,Wenliang Zhu,Cheng-Feng Qin,Baoyang Hu,Guomin Zhou +14 more
TL;DR: Variable antiviral immunity in brain organoids of different stages of culture is revealed and Preferential infection of oRGCs and differential antiviral response at various stages might explain the much more severe outcomes of JEV infection in the younger, which also provide clues to develop effective therapeutics of such diseases.
Journal ArticleDOI
FRA2A Is a CGG Repeat Expansion Associated with Silencing of AFF3
Sofie Metsu,Liesbeth Rooms,Jacqueline K. Rainger,Martin S. Taylor,Hemant Bengani,David I. Wilson,Chandra Sekhar Reddy Chilamakuri,Harris Morrison,Geert Vandeweyer,Edwin Reyniers,Evelyn Douglas,Geoffrey N. Thompson,Eric Haan,Jozef Gecz,David R. FitzPatrick,R. Frank Kooy +15 more
TL;DR: There may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here, and cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in F RA2A carriers, predicting that FRA 2A expression results in functional haploinsufficiency for Aff3 at least in a subset of tissues.
References
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