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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Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models.
TL;DR: The overall use of iPSC-based human cell models with functional cellular and biochemical assays holds promise for supporting the discovery of next-generation neuropharmacological agents for the treatment and ultimately prevention of a range of severe mental illnesses.
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Mutations in CDK5RAP2 cause Seckel syndrome.
Gökhan Yigit,Karen E. Brown,Hülya Kayserili,Esther Pohl,Almuth Caliebe,Diana Zahnleiter,Elisabeth Rosser,Nina Bögershausen,Zehra Oya Uyguner,Umut Altunoglu,Gudrun Nürnberg,Peter Nürnberg,Anita Rauch,Yun Li,Christian Thiel,Bernd Wollnik +15 more
TL;DR: It is established that loss of functional CDK5RAP2 leads to severe defects in mitosis and spindle organization, resulting in cells with abnormal nuclei and centrosomal pattern, which underlines the important role of centrosome and mitotic proteins in the pathogenesis of the disease.
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Human Cerebrospinal fluid promotes long-term neuronal viability and network function in human neocortical organotypic brain slice cultures.
Niklas Schwarz,Ulrike B. S. Hedrich,Hannah Schwarz,Harshad P.A.,Nele Maria Dammeier,Eva Auffenberg,Francesco Bedogni,Jürgen Honegger,Holger Lerche,Thomas V. Wuttke,Henner Koch +10 more
TL;DR: Human organotypic slice cultures from access tissue of resective epilepsy surgery are prepared and it is found that in contrast to artificial culturing media, hCSF significantly enhances neuron viability and maintenance of network activity.
Journal ArticleDOI
Transposable Elements: A Common Feature of Neurodevelopmental and Neurodegenerative Disorders
TL;DR: An increased understanding of the relationship between TEs and pathological processes in the brain improves the potential for novel diagnostics and interventions for brain disorders.
Journal ArticleDOI
The Ethics of Cerebral Organoid Research: Being Conscious of Consciousness
TL;DR: This paper aims to explore how cerebral organoid research is currently progressing and the future directions it is likely to take, especially in functional assessment of organoids, and how to solve ethical issues of possible consciousness in cerebral organoids.
References
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