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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Proteasome stress in skeletal muscle mounts a long-range protective response that delays retinal and brain aging
Mamta Rai,Zane Coleman,Michelle Curley,Anjana Nityanandam,Anna Platt,Maricela Robles-Murguia,Jianqin Jiao,David Finkelstein,Yong-Dong Wang,Beisi Xu,Yiping Fan,Fabio Demontis +11 more
TL;DR: In this article, the authors found that moderate perturbation of the proteasome in skeletal muscle induces compensatory preservation of CNS proteostasis during aging, which is a defining feature of organismal aging that is influenced by peripheral tissues.
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Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration
TL;DR: A review of 3D stem cell-based 3D cell culture systems generated using different engineering techniques is presented in this article , focusing on the advanced therapeutic applications of stem-cell-based 2D and 3D culture systems.
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Assessing Toxicity with Human Cell-Based In Vitro Methods.
TL;DR: In toxicology, there is a strong push towards replacing animal experiments with alternative methods, which include cell-based in vitro methods for the assessment of adverse health effects in humans, which generates new powerful tools for toxicity assessment.
Journal ArticleDOI
Axial elongation of caudalized human organoids mimics aspects of neural tube development.
Ashley R.G. Libby,Ashley R.G. Libby,David A Joy,David A Joy,Nicholas H Elder,Nicholas H Elder,Emily A Bulger,Emily A Bulger,Martina Z Krakora,Eliza A Gaylord,Frederico N. Mendoza-Camacho,Jessica C Butts,Todd C. McDevitt,Todd C. McDevitt +13 more
TL;DR: In this paper, an organoid model of neural tube extension derived from human pluripotent stem cell (hPSC) aggregates that have been caudalized with Wnt agonism was presented.
In vitro 3D Spheroids and Microtissues: ATP-based Cell Viability and Toxicity Assays
Monika Kijanska,Jens M. Kelm +1 more
TL;DR: Assessment of spheroid viability by measuring intracellular ATP content is focused on, which is equally applicable for other non-spheroid 3D tissue models to quantify viability and toxicity.
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