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Cerebral organoid

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https://www.readbyqxmd.com/read/28912154/inhibition-of-p25-cdk5-attenuates-tauopathy-in-mouse-and-ipsc-models-of-frontotemporal-dementia
#1
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 (AD). Previously, we showed that replacing endogenous p35 with the non-cleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial AD 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...
September 14, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28194309/trace-elements-during-primordial-plexiform-network-formation-in-human-cerebral-organoids
#16
Rafaela C Sartore, Simone C Cardoso, Yury V M Lages, Julia M Paraguassu, Mariana P Stelling, Rodrigo F Madeiro da Costa, Marilia Z Guimaraes, Carlos A Pérez, Stevens K Rehen
Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development in vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain...
2017: PeerJ
https://www.readbyqxmd.com/read/28157638/probing-human-brain-evolution-and-development-in-organoids
#17
REVIEW
Stefano L Giandomenico, Madeline A Lancaster
Expansion of the neocortex is thought to underpin the higher cognitive abilities of a number of mammalian lineages, such as cetaceans, elephants, and primates, with humans exhibiting a particularly enlarged and dense cerebral cortex. However, the evolutionary and developmental mechanisms that led to this expansion are not well-understood and limited to correlative observations. Historically, this has been due to technical and ethical limitations owing to the intractability of various species for functional studies...
February 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28139695/dynamic-behaviour-of-human-neuroepithelial-cells-in-the-developing-forebrain
#18
Lakshmi Subramanian, Marina Bershteyn, Mercedes F Paredes, Arnold R Kriegstein
To understand how diverse progenitor cells contribute to human neocortex development, we examined forebrain progenitor behaviour using timelapse imaging. Here we find that cell cycle dynamics of human neuroepithelial (NE) cells differ from radial glial (RG) cells in both primary tissue and in stem cell-derived organoids. NE cells undergoing proliferative, symmetric divisions retract their basal processes, and both daughter cells regrow a new process following cytokinesis. The mitotic retraction of the basal process is recapitulated by NE cells in cerebral organoids generated from human-induced pluripotent stem cells...
January 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28111201/human-ipsc-derived-cerebral-organoids-model-cellular-features-of-lissencephaly-and-reveal-prolonged-mitosis-of-outer-radial-glia
#19
Marina Bershteyn, Tomasz J Nowakowski, Alex A Pollen, Elizabeth Di Lullo, Aishwarya Nene, Anthony Wynshaw-Boris, Arnold R Kriegstein
Classical lissencephaly is a genetic neurological disorder associated with mental retardation and intractable epilepsy, and Miller-Dieker syndrome (MDS) is the most severe form of the disease. In this study, to investigate the effects of MDS on human progenitor subtypes that control neuronal output and influence brain topology, we analyzed cerebral organoids derived from control and MDS-induced pluripotent stem cells (iPSCs) using time-lapse imaging, immunostaining, and single-cell RNA sequencing. We saw a cell migration defect that was rescued when we corrected the MDS causative chromosomal deletion and severe apoptosis of the founder neuroepithelial stem cells, accompanied by increased horizontal cell divisions...
April 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28087635/retinoblastoma-protein-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#20
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
The tumor suppressor retinoblastoma protein (RB) regulates S-phase cell cycle entry via E2F transcription factors. Knockout (KO) mice have shown that RB plays roles in cell migration, differentiation and apoptosis, in developing and adult brain. In addition, the RB family is required for self-renewal and survival of human embryonic stem cells (hESCs). Since little is known about the role of RB in human brain development, we investigated its function in cerebral organoids differentiated from gene-edited hESCs lacking RB...
March 15, 2017: Development
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