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https://www.readbyqxmd.com/read/28515690/brain-renin-angiotensin-system-and-microglial-polarization-implications-for-aging-and-neurodegeneration
#1
REVIEW
Jose L Labandeira-Garcia, Ana I Rodríguez-Perez, Pablo Garrido-Gil, Jannette Rodriguez-Pallares, Jose L Lanciego, Maria J Guerra
Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28507260/reprogramming-cells-from-gulf-war-veterans-into-neurons-to-study-gulf-war-illness
#2
Liang Qiang, Anand N Rao, Gustavo Mostoslavsky, Marianne F James, Nicole Comfort, Kimberly Sullivan, Peter W Baas
Gulf War illness (GWI), which afflicts at least 25% of veterans who served in the 1990-1991 war in the Persian Gulf, is thought to be caused by deployment exposures to various neurotoxicants, including pesticides, anti-nerve gas pills, and low-level nerve agents including sarin/cyclosarin. GWI is a multisymptom disorder characterized by fatigue, joint pain, cognitive problems, and gastrointestinal complaints. The most prominent symptoms of GWI (memory problems, poor attention/concentration, chronic headaches, mood alterations, and impaired sleep) suggest that the disease primarily affects the CNS...
May 16, 2017: Neurology
https://www.readbyqxmd.com/read/28504681/fused-cerebral-organoids-model-interactions-between-brain-regions
#3
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...
May 10, 2017: Nature Methods
https://www.readbyqxmd.com/read/28490641/fetal-alcohol-exposure-reduces-responsiveness-of-taste-nerves-and-trigeminal-chemosensory-neurons-to-ethanol-and-its-flavor-components
#4
John I Glendinning, Joyce Tang, Ana Paula Morales Allende, Bruce P Bryant, Lisa Youngentob, Steven L Youngentob
Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose and NaCl...
May 10, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28480968/the-influence-of-raav2-mediated-sox2-delivery-into-neonatal-and-adult-human-rpe-cells-a-comparative-study
#5
Razie Ezati, Azadeh Etemadzadeh, Zahra-Soheila Soheili, Shahram Samiei, Ehsan Ranaei Pirmardan, Malihe Davari, Hoda Shams Najafabadi
Cell replacement is a promising therapy for degenerative diseases like age-related macular degeneration (AMD). Since the human retina lacks regeneration capacity, much attention has been directed towards persuading for cells that can differentiate into retinal neurons. In this report we have investigated reprogramming of the human RPE cells and concerned the effect of donor age on the cellular fate as a critical determinant in reprograming competence. We evaluated the effect of SOX2 over-expression in human neonatal and adult RPE cells in cultures...
May 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28472646/epigenomics-of-retinal-development-in-mice-and-humans
#6
Nicolas Lonfat, Connie Cepko
In this issue of Neuron, Aldiri et al. (2017) present an analysis of epigenetic changes during retinal development, and use these data to probe reprogramming of retinal iPSC cells, as well as the origin of retinoblastoma cells.
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28468312/induced-pluripotent-stem-cells-derived-from-a-cln5-patient-manifest-phenotypic-characteristics-of-neuronal-ceroid-lipofuscinoses
#7
Kristiina Uusi-Rauva, Tea Blom, Carina von Schantz-Fant, Tomas Blom, Anu Jalanko, Aija Kyttälä
Neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive progressive encephalopathies caused by mutations in at least 14 different genes. Despite extensive studies performed in different NCL animal models, the molecular mechanisms underlying neurodegeneration in NCLs remain poorly understood. To model NCL in human cells, we generated induced pluripotent stem cells (iPSCs) by reprogramming skin fibroblasts from a patient with CLN5 (ceroid lipofuscinosis, neuronal, 5) disease, the late infantile variant form of NCL...
May 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28455412/in-vivo-reprogramming-of-non-mammary-cells-to-an-epithelial-cell-fate-is-independent-of-amphiregulin-signaling
#8
Andrea L George, Corinne A Boulanger, Lisa H Anderson, Stéphanie Cagnet, Cathrin Brisken, Gilbert H Smith
AREG-/- mice demonstrate impaired mammary development and form only rudimentary ductal epithelial trees, however, AREG-/- glands are still capable of undergoing alveologenesis and lactogenesis during pregnancy. Transplantation of AREG-/- mammary epithelial cells into cleared mouse mammary fat pads results in a diminished capacity for epithelial growth (∼15%) as compared to wild type mammary epithelial cells. To determine whether ERα and/or AREG signaling were necessary for non-mammary cell redirection, we inoculated either ERα-/- or AREG-/- mammary cells with non-mammary progenitor cells (WapCre/Rosa26LacZ+ male testicular cells or GFP+ embryonic neuronal stem cells)...
April 28, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28452057/alternative-splicing-switches-important-players-in-cell-differentiation
#9
REVIEW
Ana Fiszbein, Alberto R Kornblihtt
Alternative splicing (AS) greatly expands the coding capacities of genomes by allowing the generation of multiple mature mRNAs from a limited number of genes. Although the massive switch in AS profiles that often accompanies variations in gene expression patterns occurring during cell differentiation has been characterized for a variety of models, their causes and mechanisms remain largely unknown. Here, we integrate foundational and recent studies indicating the AS switches that govern the processes of cell fate determination...
April 27, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28444230/apoe-%C3%AE%C2%B54-%C3%AE%C2%B54-diminishes-neurotrophic-function-of-human-ipsc-derived-astrocytes
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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)...
May 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28392217/high-throughput-and-cost-effective-characterization-of-induced-pluripotent-stem-cells
#17
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
#18
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
#19
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
#20
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
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