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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Transcriptomics analysis of iPSC-derived neurons and modeling of neuropsychiatric disorders
TL;DR: Many challenges remain in the usage of iPSC-derived neurons for modeling neuropsychiatric disorders, for example, how to generate relatively homogenous populations of specific neuronal subtypes that are affected in a particular disorder and how to better address the genetic heterogeneity that exists in the patient population.
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Scalable Production and Cryostorage of Organoids Using Core-Shell Decoupled Hydrogel Capsules.
Yen-Chun Lu,Dah-Jiun Fu,Duo An,Alan Chiu,Robert E. Schwartz,Alexander Yu. Nikitin,Minglin Ma +6 more
TL;DR: Compared with conventional, bulk ECM hydrogels, the capsules, which can be produced continuously by a two‐fluidic electrostatic cospraying method, provide better mass transfer through both diffusion and convection and leads to better cell recovery after cryopreservation of organoids probably through prevention of intracellular ice formation.
Journal ArticleDOI
Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids
Bilal Cakir,Yoshiaki Tanaka,F Ridvan Kiral,Yangfei Xiang,Onur Dagliyan,Juan Wang,Maria Lee,Allison M. Greaney,Woo Sub Yang,Catherine duBoulay,Mehmet H. Kural,Benjamin Patterson,Mei Zhong,Jonghun Kim,Yalai Bai,Wang Min,Laura E. Niklason,Prabir K. Patra,In-Hyun Park +18 more
TL;DR: In this paper , a method to generate functional microglia in human cortical organoids (hCOs) from human embryonic stem cells (hESCs) was developed, which can be used in fundamental and translational studies as a model to investigate the role of microglias in neurodevelopmental and neurodegenerative disorders.
Journal ArticleDOI
Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt-Jakob disease.
Bradley R. Groveman,Natália Ferreira,Simote T. Foliaki,Ryan O. Walters,Clayton W. Winkler,Brent Race,Andrew G. Hughson,Gianluigi Zanusso,Cathryn L. Haigh +8 more
TL;DR: In this article, the authors used human cerebral organoids as a viable model for CJD drug screening by using an established anti-prion compound, pentosan polysulfate (PPS).
Journal ArticleDOI
Human mini-brain models.
TL;DR: Methods for the creation of microphysiological human brain models that recapitulate aspects of major neurological disorders under static or dynamic conditions are discussed.
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