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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Self-organizing neuruloids model developmental aspects of Huntington's disease in the ectodermal compartment.
TL;DR: Using isogenic Huntington’s disease human embryonic stem cells and deep neural network analysis, it is shown how specific phenotypic signatures arise in this model of early human development as a consequence of mutant huntingtin protein, outlining an approach for phenotypesic drug screening.
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Strategies to improve the regulatory assessment of developmental neurotoxicity (DNT) using in vitro methods.
Anna Bal-Price,Francesca Pistollato,Magdalini Sachana,Stephanie K. Bopp,Sharon Munn,Andrew Worth +5 more
TL;DR: This work proposes to incorporate mechanistic knowledge and data derived from in vitro studies to support various regulatory applications including: the identification of potential DNT triggers, initial chemical screening and prioritization, hazard identification and characterization, and assessment of exposure to chemical mixtures.
Journal ArticleDOI
Zika virus disrupts molecular fingerprinting of human neurospheres.
Patricia P. Garcez,Juliana M. Nascimento,Janaina Mota de Vasconcelos,Rodrigo Madeiro da Costa,Rodrigo Delvecchio,Pablo Trindade,Erick Correia Loiola,Luiza M. Higa,Juliana S. Cassoli,Gabriela Vitória,Patrícia Carvalho de Sequeira,Jaroslaw Sochacki,Renato S. Aguiar,Hellen Thais Fuzii,Ana Maria Bispo de Filippis,João Lídio da Silva Gonçalves Vianez Júnior,Amilcar Tanuri,Daniel Martins-de-Souza,Stevens K. Rehen +18 more
TL;DR: Altered alterations in human neurospheres derived from induced pluripotent stem cells infected with the strain of Zika virus that is circulating in Brazil are described and point to biological mechanisms implicated in brain malformations that can be exploited as therapeutic potential targets to mitigate it.
Journal ArticleDOI
Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology
Cristina Cheroni,Cristina Cheroni,Nicolò Caporale,Nicolò Caporale,Giuseppe Testa,Giuseppe Testa +5 more
TL;DR: The transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, are outlined as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment.
Journal ArticleDOI
Concise Review: Current Status of Three-Dimensional Organoids as Preclinical Models.
TL;DR: A review of 3D organoid applications for disease modeling and drug response in different cancers can be found in this paper, where the authors discuss shortcomings, limitations, and advantages of developed 3D cultures, with the rationale behind the methodology.
References
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Journal ArticleDOI
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
Journal ArticleDOI
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
Toshiro Sato,Robert G.J. Vries,Hugo J. Snippert,Marc van de Wetering,Nick Barker,Daniel E. Stange,Johan H. van Es,Arie Abo,Pekka Kujala,Peter J. Peters,Hans Clevers +10 more
TL;DR: It is concluded that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.
Journal ArticleDOI
Generation of germline-competent induced pluripotent stem cells
TL;DR: iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.
Journal ArticleDOI
A ROCK inhibitor permits survival of dissociated human embryonic stem cells
Kiichi Watanabe,Morio Ueno,Daisuke Kamiya,Ayaka Nishiyama,Michiru Matsumura,Takafumi Wataya,Jun Takahashi,Satomi Nishikawa,Shin-Ichi Nishikawa,Keiko Muguruma,Yoshiki Sasai +10 more
TL;DR: Application of a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, to hES cells markedly diminishes dissociation-induced apoptosis, increases cloning efficiency and facilitates subcloning after gene transfer, and enables SFEB-cultured hES Cells to survive and differentiate into Bf1+ cortical and basal telencephalic progenitors.
Journal ArticleDOI
The cell biology of neurogenesis.
TL;DR: In this paper, the authors discuss how these features change during development from neuroepithelial to radial glial cells, and how this transition affects cell fate and neurogenesis.
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