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Cerebral organoid

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https://www.readbyqxmd.com/read/29118367/impaired-oxidative-stress-response-characterizes-huwe1-promoted-x-linked-intellectual-disability
#1
Matthias Bosshard, Rossana Aprigliano, Cristina Gattiker, Vuk Palibrk, Enni Markkanen, Paul Hoff Backe, Stefania Pellegrino, F Lucy Raymond, Guy Froyen, Matthias Altmeyer, Magnar Bjørås, Grigory L Dianov, Barbara van Loon
Mutations in the HECT, UBA and WWE domain-containing 1 (HUWE1) E3 ubiquitin ligase cause neurodevelopmental disorder X-linked intellectual disability (XLID). HUWE1 regulates essential processes such as genome integrity maintenance. Alterations in the genome integrity and accumulation of mutations have been tightly associated with the onset of neurodevelopmental disorders. Though HUWE1 mutations are clearly implicated in XLID and HUWE1 regulatory functions well explored, currently much is unknown about the molecular basis of HUWE1-promoted XLID...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29058117/recapitulating-cortical-development-with-organoid-culture-in-vitro-and-modeling-abnormal-spindle-like-aspm-related-primary-microcephaly-disease
#2
Rui Li, Le Sun, Ai Fang, Peng Li, Qian Wu, Xiaoqun Wang
The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases...
October 23, 2017: Protein & Cell
https://www.readbyqxmd.com/read/29020636/self-organized-cerebral-organoids-with-human-specific-features-predict-effective-drugs-to-combat-zika-virus-infection
#3
Momoko Watanabe, Jessie E Buth, Neda Vishlaghi, Luis de la Torre-Ubieta, Jiannis Taxidis, Baljit S Khakh, Giovanni Coppola, Caroline A Pearson, Ken Yamauchi, Danyang Gong, Xinghong Dai, Robert Damoiseaux, Roghiyh Aliyari, Simone Liebscher, Katja Schenke-Layland, Christine Caneda, Eric J Huang, Ye Zhang, Genhong Cheng, Daniel H Geschwind, Peyman Golshani, Ren Sun, Bennett G Novitch
The human cerebral cortex possesses distinct structural and functional features that are not found in the lower species traditionally used to model brain development and disease. Accordingly, considerable attention has been placed on the development of methods to direct pluripotent stem cells to form human brain-like structures termed organoids. However, many organoid differentiation protocols are inefficient and display marked variability in their ability to recapitulate the three-dimensional architecture and course of neurogenesis in the developing human brain...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28994790/modelling-zika-virus-infection-of-the-developing-human-brain-in-vitro-using-stem-cell-derived-cerebral-organoids
#4
Max R Salick, Michael F Wells, Kevin Eggan, Ajamete Kaykas
The recent emergence of Zika virus (ZIKV) in susceptible populations has led to an abrupt increase in microcephaly and other neurodevelopmental conditions in newborn infants. While mosquitos are the main route of viral transmission, it has also been shown to spread via sexual contact and vertical mother-to-fetus transmission. In this latter case of transmission, due to the unique viral tropism of ZIKV, the virus is believed to predominantly target the neural progenitor cells (NPCs) of the developing brain. Here a method for modeling ZIKV infection, and the resulting microcephaly, that occur when human cerebral organoids are exposed to live ZIKV is described...
September 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28993683/short-term-changes-in-the-proteome-of-human-cerebral-organoids-induced-by-5-meo-dmt
#5
Vanja Dakic, Juliana Minardi Nascimento, Rafaela Costa Sartore, Renata de Moraes Maciel, Draulio B de Araujo, Sidarta Ribeiro, Daniel Martins-de-Souza, Stevens K Rehen
Dimethyltryptamines are entheogenic serotonin-like molecules present in traditional Amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. Legal restrictions and the lack of adequate experimental models have limited the understanding of how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912154/inhibition-of-p25-cdk5-attenuates-tauopathy-in-mouse-and-ipsc-models-of-frontotemporal-dementia
#6
Jinsoo Seo, Oleg Kritskiy, L Ashley Watson, Scarlett J Barker, Dilip Dey, Waseem K Raja, Yuan-Ta Lin, Tak Ko, Sukhee Cho, Jay Penney, M Catarina Silva, Steven D Sheridan, Diane Lucente, James F Gusella, Bradford C Dickerson, Stephen J Haggarty, Li-Huei Tsai
Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders, including Alzheimer's disease. Previously, we showed that replacing endogenous p35 with the noncleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial Alzheimer's disease mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double-transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δp35KI mice...
October 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28904534/three-dimensional-organoid-system-transplantation-technologies-in-future-treatment-of-central-nervous-system-diseases
#7
REVIEW
NaiLi Wei, ZiFang Quan, Hailiang Tang, JianHong Zhu
In recent years, scientists have made great achievements in understanding the development of human brain and elucidating critical elements of stepwise spatiotemporal control strategies in neural stem cell specification lineage, which facilitates successful induction of neural organoid in vitro including the cerebral cortex, cerebellar, neural tube, hippocampus cortex, pituitary, and optic cup. Besides, emerging researches on neural organogenesis promote the application of 3D organoid system transplantation in treating central nervous system (CNS) diseases...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28777940/a-little-bit-of-guidance-mini-brains-on-their-route-to-adolescence
#8
Philipp Koch, Julia Ladewig
Cerebral organoids represent a new model in which to study human brain development outside the human body. Recently in Nature Biotechnology, Lancaster et al. (2017) tackled the lack of reproducibility, tissue homogeneity, and complexity of this system by bioengineering organoids to establish the next generation of human mini brains.
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28756233/organoid-culture-systems-to-study-host-pathogen-interactions
#9
REVIEW
Devanjali Dutta, Hans Clevers
Recent advances in host-microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered...
August 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28708059/a-tunable-refractive-index-matching-medium-for-live-imaging-cells-tissues-and-model-organisms
#10
Tobias Boothe, Lennart Hilbert, Michael Heide, Lea Berninger, Wieland B Huttner, Vasily Zaburdaev, Nadine L Vastenhouw, Eugene W Myers, David N Drechsel, Jochen C Rink
In light microscopy, refractive index mismatches between media and sample cause spherical aberrations that often limit penetration depth and resolution. Optical clearing techniques can alleviate these mismatches, but they are so far limited to fixed samples. We present Iodixanol as a non-toxic medium supplement that allows refractive index matching in live specimens and thus substantially improves image quality in live-imaged primary cell cultures, planarians, zebrafish and human cerebral organoids.
July 14, 2017: ELife
https://www.readbyqxmd.com/read/28562594/guided-self-organization-and-cortical-plate-formation-in-human-brain-organoids
#11
Madeline A Lancaster, Nina S Corsini, Simone Wolfinger, E Hilary Gustafson, Alex W Phillips, Thomas R Burkard, Tomoki Otani, Frederick J Livesey, Juergen A Knoblich
Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells or used bioengineered constructs to arrange cells in an organ-like configuration. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies...
July 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28534760/minibrain-storm-cerebral-organoids-aren-t-real-brains-but-they-provide-a-powerful-platform-for-modeling-brain-diseases-like-zika-infection-alzheimer-s-and-even-autism
#12
Shannon Fischer
Floating in a Petri dish, they look like tiny tapioca pearls in peach broth, a couple dozen in number and none much larger than the tip of a ballpoint pen. But under a microscope, dense, lumpy bodies come into focus, outlined by wispy coronas.
May 2017: IEEE Pulse
https://www.readbyqxmd.com/read/28504681/fused-cerebral-organoids-model-interactions-between-brain-regions
#13
Joshua A Bagley, Daniel Reumann, Shan Bian, Julie Lévi-Strauss, Juergen A Knoblich
Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis...
July 2017: Nature Methods
https://www.readbyqxmd.com/read/28445462/cell-diversity-and-network-dynamics-in-photosensitive-human-brain-organoids
#14
Giorgia Quadrato, Tuan Nguyen, Evan Z Macosko, John L Sherwood, Sung Min Yang, Daniel R Berger, Natalie Maria, Jorg Scholvin, Melissa Goldman, Justin P Kinney, Edward S Boyden, Jeff W Lichtman, Ziv M Williams, Steven A McCarroll, Paola Arlotta
In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina...
May 4, 2017: Nature
https://www.readbyqxmd.com/read/28439102/mecp2-regulated-mirnas-control-early-human-neurogenesis-through-differential-effects-on-erk-and-akt-signaling
#15
N Mellios, D A Feldman, S D Sheridan, J P K Ip, S Kwok, S K Amoah, B Rosen, B A Rodriguez, B Crawford, R Swaminathan, S Chou, Y Li, M Ziats, C Ernst, R Jaenisch, S J Haggarty, M Sur
Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28388422/of-mice-and-men-species-specific-organoid-models-of-neocortical-malformation
#16
COMMENT
Jesse J Dunnack, Joseph J LoTurco
Cellular changes underlying malformations of human cortical development may be difficult to identify with traditional mouse models. Two recent Cell Stem Cell papers, Li et al. (2017) and Bershteyn et al. (2017), use human cerebral organoids to identify specific cellular defects in neurogenesis that may explain PTEN-related macrocephaly and Miller-Dieker lissencephaly.
April 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28361479/a-simple-method-of-generating-3d-brain-organoids-using-standard-laboratory-equipment
#17
Magdalena Sutcliffe, Madeline A Lancaster
3D brain organoids are a powerful tool with prospective application for the study of neural development and disease. Here we describe the growth factor-free method of generating cerebral organoids from feeder-dependent or feeder-free human pluripotent stem cells using standard laboratory equipment. The protocol outlined below allows generation of 3D tissues, which replicate human early in vivo brain development up to the end of the first trimester, both in terms of morphology and gene expression pattern.
March 31, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28345587/derivation-of-functional-human-astrocytes-from-cerebral-organoids
#18
Rômulo Sperduto Dezonne, Rafaela Costa Sartore, Juliana Minardi Nascimento, Verônica M Saia-Cereda, Luciana Ferreira Romão, Soniza Vieira Alves-Leon, Jorge Marcondes de Souza, Daniel Martins-de-Souza, Stevens Kastrup Rehen, Flávia Carvalho Alcantara Gomes
Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321286/crispr-cas9-mediated-heterozygous-knockout-of-the-autism-gene-chd8-and-characterization-of-its-transcriptional-networks-in-cerebral-organoids-derived-from-ips-cells
#19
Ping Wang, Ryan Mokhtari, Erika Pedrosa, Michael Kirschenbaum, Can Bayrak, Deyou Zheng, Herbert M Lachman
BACKGROUND: CHD8 (chromodomain helicase DNA-binding protein 8), which codes for a member of the CHD family of ATP-dependent chromatin-remodeling factors, is one of the most commonly mutated genes in autism spectrum disorders (ASD) identified in exome-sequencing studies. Loss of function mutations in the gene have also been found in schizophrenia (SZ) and intellectual disabilities and influence cancer cell proliferation. We previously reported an RNA-seq analysis carried out on neural progenitor cells (NPCs) and monolayer neurons derived from induced pluripotent stem (iPS) cells that were heterozygous for CHD8 knockout (KO) alleles generated using CRISPR-Cas9 gene editing...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28283582/self-organized-developmental-patterning-and-differentiation-in-cerebral-organoids
#20
Magdalena Renner, Madeline A Lancaster, Shan Bian, Heejin Choi, Taeyun Ku, Angela Peer, Kwanghun Chung, Juergen A Knoblich
Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia...
May 15, 2017: EMBO Journal
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