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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Convergence of microengineering and cellular self-organization towards functional tissue manufacturing
Jérémie Laurent,Guillaume Blin,Francois Chatelain,Francois Chatelain,Valérie Vanneaux,Alexandra Fuchs,Alexandra Fuchs,Jérôme Larghero,Manuel Théry,Manuel Théry +9 more
TL;DR: It is argued that tissue-manufacturing approaches relying on directed self-organization will enable the production of functional tissues with complex biological features and is a promising direction for the manufacturing of complex functional tissues.
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Emergence and Developmental Roles of the Cerebrospinal Fluid System.
Ryann M. Fame,Maria K. Lehtinen +1 more
TL;DR: This review examines the current understanding about early CSF and its maturation and roles during CNS development and discusses open questions in the field, focusing on developmental changes in the ventricular system and CSF sources.
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Modeling psychiatric disorders for developing effective treatments.
TL;DR: This paper reviewed recent advances in modeling psychiatric disease, discuss the utility and limitations of animal models, and emphasize the importance of shifting from behavioral analysis to identifying neurophysiological abnormalities, which are likely to be more conserved across species and thus may increase translatability.
Journal ArticleDOI
Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids
Ann Na Cho,Yoonhee Jin,Yeonjoo An,Jin Kim,Yi Sun Choi,Jung Seung Lee,Jung-Hoon Kim,Won-Young Choi,Dong-Jun Koo,Weonjin Yu,Gyeong-Eon Chang,Dongyoon Kim,Sung-Hyun Jo,Ji Hun Kim,Sung-Yon Kim,Yun-Gon Kim,Ju-Young Kim,Nakwon Choi,Eunji Cheong,Young Joon Kim,Hyunsoo Shawn Je,Hoon Chul Kang,Seung Woo Cho +22 more
TL;DR: In this paper, a human brain extracellular matrix was used to provide brain-specific cues and a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids.
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Generation of "Off-the-Shelf" Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells.
TL;DR: A practical “from blood cell to stem cells and back with less (less KIRs)” strategy to generate abundant “universal” NK cells from PBC-iPSCs for a wide range of patients is established.
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