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https://www.readbyqxmd.com/read/28444230/apoe-%C3%AE%C2%B54-%C3%AE%C2%B54-diminishes-neurotrophic-function-of-human-ipsc-derived-astrocytes
#1
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/28440665/reprogramming-of-oncogene-expression-in-gingival-mesenchymal-stem-cells-following-long-term-culture-in-vitro
#2
Agnese Gugliandolo, Thangavelu Soundara Rajan, Domenico Scionti, Francesca Diomede, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Mesenchymal stem cells (MSCs) are a promising resource for stem cell therapy for the treatment of different neurodegenerative disorders. In particular, dental MSCs, given their origin from neural crest and their proneness toward neuronal differentiation, may be more suitable for transplantation. However, if MSCs can undergo spontaneous transformation and give rise to tumor is still debated. Data about transcriptional regulation of oncogenes in MSCs following in vitro expansion are not available. In this work, we compared gene expression levels of oncogenes in gingival-derived MSCs at passage number 10 and 41...
April 25, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28435980/-glial-cells-function-as-neural-stem-cells-and-progenitor-cells
#3
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/28430167/induced-pluripotent-stem-cell-modeling-of-gaucher-s-disease-what-have-we-learned
#4
REVIEW
Dino Matias Santos, Gustavo Tiscornia
Gaucher's disease (GD) is the most frequently inherited lysosomal storage disease, presenting both visceral and neurologic symptoms. Mutations in acid β-glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, neither of these approaches is effective in treating the neurological aspect of the disease. The use of small pharmacological compounds that act as molecular chaperones is a promising approach that is still experimental...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28413817/dataset-in-support-of-the-generation-of-niemann-pick-disease-type-c1-patient-specific-ips-cell-lines-carrying-the-novel-npc1-mutation-c-1180t-c-or-the-prevalent-c-3182t-c-mutation-analysis-of-pluripotency-and-neuronal-differentiation
#5
Franziska Peter, Michaela Trilck, Michael Rabenstein, Arndt Rolfs, Moritz J Frech
Data presented in this article demonstrate the generation and characterization of two novel Niemann-Pick disease Type C1 (NPC1) patient-specific induced pluripotent stem cell (iPSC) lines, related to the research article Trilck et al. (Diversity of Glycosphingolipid GM2 and Cholesterol Accumulation in NPC1 Patient-Specific iPSC-Derived Neurons; Brain Res.; 2017; 1657:52-61. doi: 10.1016/j.brainres.2016.11.031). For reprogramming fibroblasts, carrying the novel homozygous mutation c.1180T>C and the prevalent homozygous mutation c...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28410643/high-throughput-and-cost-effective-characterization-of-induced-pluripotent-stem-cells
#6
Matteo D'Antonio, Grace Woodruff, Jason L Nathanson, Agnieszka D'Antonio-Chronowska, Angelo Arias, Hiroko Matsui, Roy Williams, Cheryl Herrera, Sol M Reyna, Gene W Yeo, Lawrence S B Goldstein, Athanasia D Panopoulos, Kelly A Frazer
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published that use small panels of iPSC-derived cell lines to study monogenic diseases. However, to study complex diseases, where the genetic variation underlying the disorder is unknown, a sizable number of patient-specific iPSC lines and controls need to be generated...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28398344/induction-of-functional-dopamine-neurons-from-human-astrocytes-in-vitro-and-mouse-astrocytes-in-a-parkinson-s-disease-model
#7
Pia Rivetti di Val Cervo, Roman A Romanov, Giada Spigolon, Débora Masini, Elisa Martín-Montañez, Enrique M Toledo, Gioele La Manno, Michael Feyder, Christian Pifl, Yi-Han Ng, Sara Padrell Sánchez, Sten Linnarsson, Marius Wernig, Tibor Harkany, Gilberto Fisone, Ernest Arenas
Cell replacement therapies for neurodegenerative disease have focused on transplantation of the cell types affected by the pathological process. Here we describe an alternative strategy for Parkinson's disease in which dopamine neurons are generated by direct conversion of astrocytes. Using three transcription factors, NEUROD1, ASCL1 and LMX1A, and the microRNA miR218, collectively designated NeAL218, we reprogram human astrocytes in vitro, and mouse astrocytes in vivo, into induced dopamine neurons (iDANs)...
April 10, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28392217/high-throughput-and-cost-effective-characterization-of-induced-pluripotent-stem-cells
#8
Matteo D'Antonio, Grace Woodruff, Jason L Nathanson, Agnieszka D'Antonio-Chronowska, Angelo Arias, Hiroko Matsui, Roy Williams, Cheryl Herrera, Sol M Reyna, Gene W Yeo, Lawrence S B Goldstein, Athanasia D Panopoulos, Kelly A Frazer
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published that use small panels of iPSC-derived cell lines to study monogenic diseases. However, to study complex diseases, where the genetic variation underlying the disorder is unknown, a sizable number of patient-specific iPSC lines and controls need to be generated...
April 4, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28386218/control-of-mrna-translation-in-als-proteinopathy
#9
REVIEW
Gianluca Cestra, Simona Rossi, Michela Di Salvio, Mauro Cozzolino
Cells robustly reprogram gene expression during stress generated by protein misfolding and aggregation. In this condition, cells assemble the bulk of mRNAs into translationally silent stress granules (SGs), while they sustain the translation of specific mRNAs coding for proteins that are needed to overcome cellular stress. Alterations of this process are deeply associated to neurodegeneration. This is the case of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder caused by a selective loss of motor neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28385536/mining-the-topography-and-dynamics-of-the-4d-nucleome-to-identify-novel-cns-drug-pathways
#10
Gerald A Higgins, Ari Allyn-Feuer, Patrick Georgoff, Vahagn Nikolian, Hasan Alam, Brian D Athey
The pharmacoepigenome can be defined as the active, noncoding province of the genome including canonical spatial and temporal regulatory mechanisms of gene regulation that respond to xenobiotic stimuli. Many psychotropic drugs that have been in clinical use for decades have ill-defined mechanisms of action that are beginning to be resolved as we understand the transcriptional hierarchy and dynamics of the nucleus. In this review, we describe spatial, temporal and biomechanical mechanisms mediated by psychotropic medications...
April 3, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28379941/myt1l-safeguards-neuronal-identity-by-actively-repressing-many-non-neuronal-fates
#11
Moritz Mall, Michael S Kareta, Soham Chanda, Henrik Ahlenius, Nicholas Perotti, Bo Zhou, Sarah D Grieder, Xuecai Ge, Sienna Drake, Cheen Euong Ang, Brandon M Walker, Thomas Vierbuchen, Daniel R Fuentes, Philip Brennecke, Kazuhiro R Nitta, Arttu Jolma, Lars M Steinmetz, Jussi Taipale, Thomas C Südhof, Marius Wernig
Normal differentiation and induced reprogramming require the activation of target cell programs and silencing of donor cell programs. In reprogramming, the same factors are often used to reprogram many different donor cell types. As most developmental repressors, such as RE1-silencing transcription factor (REST) and Groucho (also known as TLE), are considered lineage-specific repressors, it remains unclear how identical combinations of transcription factors can silence so many different donor programs. Distinct lineage repressors would have to be induced in different donor cell types...
April 13, 2017: Nature
https://www.readbyqxmd.com/read/28377600/low-level-laser-facilitates-alternatively-activated-macrophage-microglia-polarization-and-promotes-functional-recovery-after-crush-spinal-cord-injury-in-rats
#12
Ji Wei Song, Kun Li, Zhuo Wen Liang, Chen Dai, Xue Feng Shen, Yu Ze Gong, Shuang Wang, Xue Yu Hu, Zhe Wang
Macrophages and resident microglia play an import role in the secondary neuroinflammation response following spinal cord injury. Reprogramming of macrophage/microglia polarization is an import strategy for spinal cord injury restoration. Low-level laser therapy (LLLT) is a noninvasive treatment that has been widely used in neurotrauma and neurodegenerative diseases. However, the influence of low-level laser on polarization of macrophage/microglia following spinal cord injury remains unknown. The present study applied low-level laser therapy on a crush spinal cord injury rat model...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373553/memory-of-recent-oxygen-experience-switches-pheromone-valence-in-caenorhabditis-elegans
#13
Lorenz A Fenk, Mario de Bono
Animals adjust their behavioral priorities according to momentary needs and prior experience. We show that Caenorhabditis elegans changes how it processes sensory information according to the oxygen environment it experienced recently. C. elegans acclimated to 7% O2 are aroused by CO2 and repelled by pheromones that attract animals acclimated to 21% O2 This behavioral plasticity arises from prolonged activity differences in a circuit that continuously signals O2 levels. A sustained change in the activity of O2-sensing neurons reprograms the properties of their postsynaptic partners, the RMG hub interneurons...
April 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28356547/mechanisms-of-ips-cell-generation-and-beyond
#14
Keisuke Kaji
The generation of induced pluripotent stem cells (iPSCs) achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc, transformed our classical views of the cellular epigenetic landscape and delivered a new concept for cell and tissue engineering. In addition to iPSCs, several other cell types have also been generated by master transcription factor (TF)-mediated transdifferentiation. However, the critical molecular mechanisms amongst diverse cellular identity changes are not well understood. Through the investigation of reprogramming mechanisms, we recently revealed that over-expression of constitutive active Smad3 boosted not only iPSC generation, but also 3 other master TF-mediated conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons...
2017: Keio Journal of Medicine
https://www.readbyqxmd.com/read/28353247/combining-patient-reprogrammed-neural-cells-and-proteomics-as-a-model-to-study-psychiatric-disorders
#15
Giuliana S Zuccoli, Daniel Martins-de-Souza, Paul C Guest, Stevens K Rehen, Juliana Minardi Nascimento
The mechanisms underlying the pathophysiology of psychiatric disorders are still poorly known. Most of the studies about these disorders have been conducted on postmortem tissue or in limited preclinical models. The development of human induced pluripotent stem cells (iPSCs) has helped to increase the translational capacity of molecular profiling studies of psychiatric disorders through provision of human neuronal-like tissue. This approach consists of generation of pluripotent cells by genetically reprogramming somatic cells to produce the multiple neural cell types as observed within the nervous tissue...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28346452/purine-synthesis-promotes-maintenance-of-brain-tumor-initiating-cells-in-glioma
#16
Xiuxing Wang, Kailin Yang, Qi Xie, Qiulian Wu, Stephen C Mack, Yu Shi, Leo J Y Kim, Briana C Prager, William A Flavahan, Xiaojing Liu, Meromit Singer, Christopher G Hubert, Tyler E Miller, Wenchao Zhou, Zhi Huang, Xiaoguang Fang, Aviv Regev, Mario L Suvà, Tae Hyun Hwang, Jason W Locasale, Shideng Bao, Jeremy N Rich
Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility...
May 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28345605/extracellular-matrix-protein-reelin-promotes-myeloma-progression-by-facilitating-tumor-cell-proliferation-and-glycolysis
#17
Xiaodan Qin, Liang Lin, Li Cao, Xinwei Zhang, Xiao Song, Jie Hao, Yan Zhang, Risheng Wei, Xiaojun Huang, Jin Lu, Qing Ge
Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negatively associated with myeloma prognosis. Reelin promotes myeloma cell proliferation in vitro as well as in vivo. The Warburg effect, evidenced by increased glucose uptake and lactate production, is also enhanced in Reelin-expressing cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344001/inducible-and-deterministic-forward-programming-of-human-pluripotent-stem-cells-into-neurons-skeletal-myocytes-and-oligodendrocytes
#18
Matthias Pawlowski, Daniel Ortmann, Alessandro Bertero, Joana M Tavares, Roger A Pedersen, Ludovic Vallier, Mark R N Kotter
The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#19
Tasleem Arif, Yakov Kerlin, Itay Nakdimon, Daniel Benharroch, Avijit Paul, Daniela Dadon-Klein, Varda Shoshan-Barmatz
Background.: Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis. Methods...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28336360/gain-a-graphical-method-to-automatically-analyze-individual-neurite-outgrowth
#20
B L Long, H Li, A Mahadevan, T Tang, K Balotin, N Grandel, J Soto, S Y Wong, A Abrego, S Li, A A Qutub
BACKGROUND: Neurite outgrowth is a metric widely used to assess the success of in vitro neural stem cell differentiation or neuron reprogramming protocols and to evaluate high-content screening assays for neural regenerative drug discovery. However, neurite measurements are tedious to perform manually, and there is a paucity of freely available, fully automated software to determine neurite measurements and neuron counting. To provide such a tool to the neurobiology, stem cell, cell engineering, and neuroregenerative communities, we developed an algorithm for performing high-throughput neurite analysis in immunofluorescent images...
March 21, 2017: Journal of Neuroscience Methods
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