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https://www.readbyqxmd.com/read/28448519/zika-infection-of-neural-progenitor-cells-perturbs-transcription-in-neurodevelopmental-pathways
#1
Lynn Yi, Harold Pimentel, Lior Pachter
BACKGROUND: A recent study of the gene expression patterns of Zika virus (ZIKV) infected human neural progenitor cells (hNPCs) revealed transcriptional dysregulation and identified cell cycle-related pathways that are affected by infection. However deeper exploration of the information present in the RNA-Seq data can be used to further elucidate the manner in which Zika infection of hNPCs affects the transcriptome, refining pathway predictions and revealing isoform-specific dynamics. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data published by Tang et al...
2017: PloS One
https://www.readbyqxmd.com/read/28448440/is-polysialylated-ncam-not-only-a-regulator-during-brain-development-but-also-during-the-formation-of-other-organs
#2
REVIEW
Christina E Galuska, Thomas Lütteke, Sebastian P Galuska
In mammals several cell adhesion molecules are involved during the pre- and postnatal development of all organ systems. A very prominent member of this family is the neural cell adhesion molecule (NCAM). Interestingly, NCAM can be a target for a special form of posttranslational modification: polysialylation. Whereas nearly all extracellular proteins bear mono-sialic acid residues, only a very small group can be polysialylated. Polysialic acid is a highly negatively-charged sugar polymer and can comprise more than 90 sialic acid residues in postnatal mouse brains increasing dramatically the hydrodynamic radius of their carriers...
April 27, 2017: Biology
https://www.readbyqxmd.com/read/28448044/generation-of-ipsc-derived-human-brain-organoids-to-model-early-neurodevelopmental-disorders
#3
Elke Gabriel, Jay Gopalakrishnan
The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28448009/using-primary-neurosphere-cultures-to-study-primary-cilia
#4
Issei S Shimada, Hemant Badgandi, Bandarigoda N Somatilaka, Saikat Mukhopadhyay
The primary cilium is fundamentally important for the proliferation of neural stem/progenitor cells and for neuronal differentiation during embryonic, postnatal, and adult life. In addition, most differentiated neurons possess primary cilia that house signaling receptors, such as G-protein-coupled receptors, and signaling molecules, such as adenylyl cyclases. The primary cilium determines the activity of multiple developmental pathways, including the sonic hedgehog pathway during embryonic neuronal development, and also functions in promoting compartmentalized subcellular signaling during adult neuronal function...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28446817/shh-mediated-centrosomal-recruitment-of-pka-promotes-symmetric-proliferative-neuroepithelial-cell%C3%A2-division
#5
Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto, Elisa Martí
Tight control of the balance between self-expanding symmetric and self-renewing asymmetric neural progenitor divisions is crucial to regulate the number of cells in the developing central nervous system. We recently demonstrated that Sonic hedgehog (Shh) signalling is required for the expansion of motor neuron progenitors by maintaining symmetric divisions. Here we show that activation of Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions...
April 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28444230/apoe-%C3%AE%C2%B54-%C3%AE%C2%B54-diminishes-neurotrophic-function-of-human-ipsc-derived-astrocytes
#6
Jing Zhao, Mary D Davis, Yuka Atagi, Mitsuru Shinohara, Neill R Graff-Radford, Steven G Younkin, Zbigniew K Wszolek, Takahisa Kanekiyo, Guojun Bu
The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipids including cholesterol to support neuronal homeostasis and synaptic integrity. Although mouse models and corresponding primary cells have provided valuable tools for studying apoE isoform-dependent functions, recent studies have shown that human astrocytes have distinct gene expression profile compare with rodent astrocytes...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28442710/lsh-hells-regulates-self-renewal-proliferation-of-neural-stem-progenitor-cells
#7
Yixing Han, Jianke Ren, Eunice Lee, Xiaoping Xu, Weishi Yu, Kathrin Muegge
Epigenetic mechanisms are known to exert control over gene expression and determine cell fate. Genetic mutations in epigenetic regulators are responsible for several neurologic disorders. Mutations of the chromatin remodeling protein Lsh/HELLS can cause the human Immunodeficiency, Centromere instability and Facial anomalies (ICF) syndrome, which is associated with neurologic deficiencies. We report here a critical role for Lsh in murine neural development. Lsh depleted neural stem/progenitor cells (NSPCs) display reduced growth, increases in apoptosis and impaired ability of self-renewal...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442356/unbiased-stereological-analysis-of-the-fate-of-oligodendrocyte-progenitor-cells-in-the-adult-mouse-brain-and-effect-of-reference-memory-training
#8
Jenna J Boulanger, Claude Messier
Oligodendrocyte progenitor cells (OPC) are glial cells that differentiate into myelinating oligodendrocytes during early stages of post-natal life. However, OPCs persist beyond developmental myelination and represent an important population of cycling cells in the grey and white matter of the adult brain. Here, we used unbiased systematic stereological analysis to determine the total number of OPCs in the neocortex and corpus callosum of the adult mouse. We found that the ratio of OPCs to neurons is of 1: 10 in the adult neocortex...
April 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28441409/a-hypomorphic-piga-gene-mutation-causes-severe-defects-in-neuron-development-and-susceptibility-to-complement-mediated-toxicity-in-a-human-ipsc-model
#9
Xuan Yuan, Zhe Li, Andrea C Baines, Eleni Gavriilaki, Zhaohui Ye, Zhexing Wen, Evan M Braunstein, Leslie G Biesecker, Linzhao Cheng, Xinzhong Dong, Robert A Brodsky
Mutations in genes involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis underlie a group of congenital syndromes characterized by severe neurodevelopmental defects. GPI anchored proteins have diverse roles in cell adhesion, signaling, metabolism and complement regulation. Over 30 enzymes are required for GPI anchor biosynthesis and PIGA is involved in the first step of this process. A hypomorphic mutation in the X-linked PIGA gene (c.1234C>T) causes multiple congenital anomalies hypotonia seizure syndrome 2 (MCAHS2), indicating that even partial reduction of GPI anchored proteins dramatically impairs central nervous system development, but the mechanism is unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28440805/cell-transplantation-therapy-for-spinal-cord-injury
#10
REVIEW
Peggy Assinck, Greg J Duncan, Brett J Hilton, Jason R Plemel, Wolfram Tetzlaff
Spinal cord injury can lead to severe motor, sensory and autonomic dysfunction. Currently, there is no effective treatment for the injured spinal cord. The transplantation of Schwann cells, neural stem cells or progenitor cells, olfactory ensheathing cells, oligodendrocyte precursor cells and mesenchymal stem cells has been investigated as potential therapies for spinal cord injury. However, little is known about the mechanisms through which these individual cell types promote repair and functional improvements...
April 25, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28440309/glypican-2-levels-in-cerebrospinal-fluid-predict-the-status-of-adult-hippocampal-neurogenesis
#11
S Lugert, T Kremer, R Jagasia, A Herrmann, S Aigner, C Giachino, I Mendez-David, A M Gardier, J P Carralot, H Meistermann, A Augustin, M D Saxe, J Lamerz, G Duran-Pacheco, A Ducret, V Taylor, D J David, C Czech
Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439102/mecp2-regulated-mirnas-control-early-human-neurogenesis-through-differential-effects-on-erk-and-akt-signaling
#12
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/28438991/differentiation-of-v2a-interneurons-from-human-pluripotent-stem-cells
#13
Jessica C Butts, Dylan A McCreedy, Jorge Alexis Martinez-Vargas, Frederico N Mendoza-Camacho, Tracy A Hookway, Casey A Gifford, Praveen Taneja, Linda Noble-Haeusslein, Todd C McDevitt
The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10(+) V2a interneurons from human pluripotent stem cells (hPSCs)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438527/the-baf-brg1-brm-associated-factor-chromatin-remodeling-complex-exhibits-ethanol-sensitivity-in-fetal-neural-progenitor-cells-and-regulates-transcription-at-the-mir-9-2-encoding-gene-locus
#14
Sasha G Burrowes, Nihal A Salem, Alexander M Tseng, Sridevi Balaraman, Marisa R Pinson, Cadianna Garcia, Rajesh C Miranda
Fetal alcohol spectrum disorders are a leading cause of intellectual disability worldwide. Previous studies have shown that developmental ethanol exposure results in loss of microRNAs (miRNAs), including miR-9, and loss of these miRNAs, in turn, mediates some of ethanol's teratogenic effects in the developing brain. We previously found that ethanol increased methylation at the miR-9-2 encoding gene locus in mouse fetal neural stem cells (NSC), advancing a mechanism for epigenetic silencing of this locus and consequently, miR-9 loss in NSCs...
April 7, 2017: Alcohol
https://www.readbyqxmd.com/read/28435980/-glial-cells-function-as-neural-stem-cells-and-progenitor-cells
#15
Zi-Jian Tan, Shu-Hui Ju, Xiao Huang, Ya-Kun Gu, Zhi-Da Su
Glial cells, including astrocytes, oligodendrocyte progenitor cells (OPCs), NG2-glia, etc, are broadly distributed throughout the central nervous system (CNS). Also, it has been well known that glial cells play multi-roles in physiological and pathological processes in the CNS, such as maintaining homeostasis, providing neurotrophins for neurons and regulating neural signal transmission. Recently, increasing evidence showed that glial cells may also function as neural stem/progenitor cells and contribute to adult neurogenesis or neuroregeneration...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28434858/stem-cell-intrinsic-seven-up-triggered-temporal-factor-gradients-diversify-intermediate-neural-progenitors
#16
Qingzhong Ren, Ching-Po Yang, Zhiyong Liu, Ken Sugino, Kent Mok, Yisheng He, Masayoshi Ito, Aljoscha Nern, Hideo Otsuna, Tzumin Lee
Building a sizable, complex brain requires both cellular expansion and diversification. One mechanism to achieve these goals is production of multiple transiently amplifying intermediate neural progenitors (INPs) from a single neural stem cell. Like mammalian neural stem cells, Drosophila type II neuroblasts utilize INPs to produce neurons and glia. Within a given lineage, the consecutively born INPs produce morphologically distinct progeny, presumably due to differential inheritance of temporal factors. To uncover the underlying temporal fating mechanisms, we profiled type II neuroblasts' transcriptome across time...
April 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28434801/netrin1-produced-by-neural-progenitors-not-floor-plate-cells-is-required-for-axon-guidance-in-the-spinal-cord
#17
Supraja G Varadarajan, Jennifer H Kong, Keith D Phan, Tzu-Jen Kao, S Carmen Panaitof, Julie Cardin, Holger Eltzschig, Artur Kania, Bennett G Novitch, Samantha J Butler
Netrin1 has been proposed to act from the floor plate (FP) as a long-range diffusible chemoattractant for commissural axons in the embryonic spinal cord. However, netrin1 mRNA and protein are also present in neural progenitors within the ventricular zone (VZ), raising the question of which source of netrin1 promotes ventrally directed axon growth. Here, we use genetic approaches in mice to selectively remove netrin from different regions of the spinal cord. Our analyses show that the FP is not the source of netrin1 directing axons to the ventral midline, while local VZ-supplied netrin1 is required for this step...
April 20, 2017: Neuron
https://www.readbyqxmd.com/read/28434226/in-situ-microprobe-single-cell-capillary-electrophoresis-mass-spectrometry-metabolic-reorganization-in-single-differentiating-cells-in-the-live-vertebrate-x-laevis-embryo
#18
Rosemary M Onjiko, Erika P Portero, Sally A Moody, Peter Nemes
Knowledge of single-cell metabolism would provide a powerful window to cell activity changes as cells differentiate to all the tissues of the vertebrate embryo. However, single-cell mass spectrometry technologies have not yet been made compatible with complex three-dimensional changes and rapidly decreasing cell sizes during early development of the embryo. Here, we bridge this technological gap by integrating capillary microsampling, microscale metabolite extraction, and capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI-MS) to enable direct metabolic metabolic analysis of identified cells in the live frog embryo (Xenopus laevis)...
April 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28434166/antibody-uptake-assay-in-the-embryonic-zebrafish-forebrain-to-study-notch-signaling-dynamics-in-neural-progenitor-cells-in-vivo
#19
Kai Tong, Mahendra Wagle, Su Guo
Stem cells can generate cell fate heterogeneity through asymmetric cell division (ACD). ACD derives from the asymmetric segregation of fate-determining molecules and/or organelles in the dividing cell. Radial glia in the embryonic zebrafish forebrain are an excellent model for studying the molecular mechanisms regulating ACD of stem cells in vertebrates, especially for live imaging concerning in vivo molecular and cellular dynamics. Due to the current difficulty in expressing fluorescent reporter-tagged proteins at physiological levels in zebrafish for live imaging, we have developed an antibody uptake assay to label proteins in live embryonic zebrafish forebrain with high specificity...
April 23, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28432214/a-microrna-mrna-expression-network-during-oral-siphon-regeneration-in-ciona
#20
Elijah J Spina, Elmer Guzman, Hongjun Zhou, Kenneth S Kosik, William C Smith
Here we present a parallel study of mRNA and microRNA expression during oral siphon (OS) regeneration in Ciona robusta, and the derived network of their interactions. In the process of identifying 248 mRNAs and 15 microRNAs as differentially expressed (DE), we also identified 57 novel microRNAs, several of which are among the most highly DE. Analysis of functional categories identified enriched transcripts related to stress responses and apoptosis at the wound healing stage, signaling pathways including Wnt and TGF-β during early regrowth, and negative regulation of extracellular proteases in late stage regeneration...
April 21, 2017: Development
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