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https://www.readbyqxmd.com/read/28238795/reversal-of-phenotypic-abnormalities-by-crispr-cas9-mediated-gene-correction-in-huntington-disease-patient-derived-induced-pluripotent-stem%C3%A2-cells
#1
Xiaohong Xu, Yilin Tay, Bernice Sim, Su-In Yoon, Yihui Huang, Jolene Ooi, Kagistia Hana Utami, Amin Ziaei, Bryan Ng, Carola Radulescu, Donovan Low, Alvin Yu Jin Ng, Marie Loh, Byrappa Venkatesh, Florent Ginhoux, George J Augustine, Mahmoud A Pouladi
Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT. Here we report correction of HD human induced pluripotent stem cells (hiPSCs) using a CRISPR-Cas9 and piggyBac transposon-based approach. We show that both HD and corrected isogenic hiPSCs can be differentiated into excitable, synaptically active forebrain neurons. We further demonstrate that phenotypic abnormalities in HD hiPSC-derived neural cells, including impaired neural rosette formation, increased susceptibility to growth factor withdrawal, and deficits in mitochondrial respiration, are rescued in isogenic controls...
February 21, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28238143/electrospun-nanofiber-scaffolds-and-their-hydrogel-composites-for-the-engineering-and-regeneration-of-soft-tissues
#2
Ohan S Manoukian, Rita Matta, Justin Letendre, Paige Collins, Augustus D Mazzocca, Sangamesh G Kumbar
Electrospinning has emerged as a simple, elegant, and scalable technique that can be used to fabricate polymeric nanofibers. Pure polymers as well as blends and composites of both natural and synthetic ones have been successfully electrospun into nanofiber matrices for many biomedical applications. Tissue-engineered medical implants, such as polymeric nanofiber scaffolds, are potential alternatives to autografts and allografts, which are short in supply and carry risks of disease transmission. These scaffolds have been used to engineer various soft tissues, including connective tissues, such as skin, ligament, and tendon, as well as nonconnective ones, such as vascular, muscle, and neural tissue...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28237361/corrigendum-to-a-combination-of-small-molecules-directly-reprograms-mouse-fibroblasts-into-neural-stem-cells-biochem-biophys-res-commun-476-2016-42-48
#3
Jie Zheng, Kyung-Ah Choi, Phil Jun Kang, Solji Hyeon, Suhyun Kwon, Jai-Hee Moon, Insik Hwang, Yang In Kim, Yoon Sik Kim, Byung Sun Yoon, Gyuman Park, JangBo Lee, SungHoi Hong, Seungkwon You
No abstract text is available yet for this article.
February 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28235409/acetazolamide-potentiates-the-anti-tumor-potential-of-hdaci-ms-275-in-neuroblastoma
#4
Reza Bayat Mokhtari, Narges Baluch, Micky Ka Hon Tsui, Sushil Kumar, Tina S Homayouni, Karen Aitken, Bikul Das, Sylvain Baruchel, Herman Yeger
BACKGROUND: Neuroblastoma (NB), a tumor of the primitive neural crest, despite aggressive treatment portends a poor long-term survival for patients with advanced high stage NB. New treatment strategies are required. METHODS: We investigated coordinated targeting of essential homeostatic regulatory factors involved in cancer progression, histone deacetylases (HDACs) and carbonic anhydrases (CAs). RESULTS: We evaluated the antitumor potential of the HDAC inhibitor (HDACi), pyridylmethyl-N-{4-[(2-aminophenyl)-carbamoyl]-benzyl}-carbamate (MS-275) in combination with a pan CA inhibitor, acetazolamide (AZ) on NB SH-SY5Y, SK-N-SH and SK-N-BE(2) cells...
February 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28231465/time-specific-effects-of-spindle-positioning-on-embryonic-progenitor-pool-composition-and-adult-neural-stem-cell-seeding
#5
Sven Falk, Stéphane Bugeon, Jovica Ninkovic, Gregor-Alexander Pilz, Maria Pia Postiglione, Harold Cremer, Jürgen A Knoblich, Magdalena Götz
The developmental mechanisms regulating the number of adult neural stem cells (aNSCs) are largely unknown. Here we show that the cleavage plane orientation in murine embryonic radial glia cells (RGCs) regulates the number of aNSCs in the lateral ganglionic eminence (LGE). Randomizing spindle orientation in RGCs by overexpression of Insc or a dominant-negative form of Lgn (dnLgn) reduces the frequency of self-renewing asymmetric divisions while favoring symmetric divisions generating two SNPs. Importantly, these changes during embryonic development result in reduced seeding of aNSCs...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28231457/a-butterfly-effect-on-neural-stem-cells
#6
Pierre Vanderhaeghen
Adult neural stem cells originate from the embryonic brain, but the underlying mechanisms remain poorly known. In this issue of Neuron, Falk et al. (2017) reveal how the timely control of cleavage plane orientation during division of embryonic neural progenitors has a specific and long-lasting impact on adult neurogenesis.
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28230278/deletion-of-psychiatric-risk-gene-cacna1c-impairs-hippocampal-neurogenesis-in-cell-autonomous-fashion
#7
Bianca Völkening, Kai Schönig, Golo Kronenberg, Dusan Bartsch, Tillmann Weber
Ca(2+) is a universal signal transducer which fulfills essential functions in cell development and differentiation. CACNA1C, the gene encoding the alpha-1C subunit (i.e., Cav 1.2) of the voltage-dependent l-type calcium channel (LTCC), has been implicated as a risk gene in a variety of neuropsychiatric disorders. To parse the role of Cav 1.2 channels located on astrocyte-like stem cells and their descendants in the development of new granule neurons, we created Tg(GLAST-CreERT2) /Cacna1c(fl/fl) /RCE:loxP mice, a transgenic tool that allows cell-type-specific inducible deletion of Cacna1c...
February 23, 2017: Glia
https://www.readbyqxmd.com/read/28229087/modeling-williams-syndrome-with-induced-pluripotent-stem-cells
#8
Thanathom Chailangkarn, Alysson R Muotri
The development of induced pluripotent stem cells (iPSCs) like never before has opened novel opportunity to study diseases in relevant cell types. In our recent study, Williams syndrome (WS), a rare genetic neurodevelopmental disorder, that is caused by hemizygous deletion of 25-28 genes on chromosome 7, is of interest because of its unique cognitive and social profiles. Little is known about haploinsufficiency effect of those deleted genes on molecular and cellular phenotypes at the neural level due to the lack of relevant human cellular model...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28229086/rb-an-essential-player-in-adult-neurogenesis
#9
Bensun C Fong, Ruth S Slack
The fundamental mechanisms underlying adult neurogenesis remain to be fully clarified. Members of the cell cycle machinery have demonstrated key roles in regulating adult neural stem cell (NSC) quiescence and the size of the adult-born neuronal population. The retinoblastoma protein, Rb, is known to possess CNS-specific requirements that are independent from its classical role as a tumor suppressor. The recent study by Vandenbosch et al. has clarified distinct requirements for Rb during adult neurogenesis, in the restriction of proliferation, as well as long-term adult-born neuronal survival...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28229085/folate-receptor-alpha-is-more-than-just-a-folate-transporter
#10
Vineet Mohanty, M Rizwan Siddiqui, Tadanori Tomita, Chandra Shekhar Mayanil
Until recently folate receptor alpha (FRα) has only been considered as a folate transporter. However, a novel role of FRα as a transcription factor was reported by our lab. More recently our lab showed a novel pleiotropic role of FRα: (a) direct transcriptional activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules. These observations beg a question: "Can a simple molecule such as folate be used to manipulate the production and/or differentiation of endogenous neural stem cells (NSCs), which may hold promise for future therapies?" Conditions such as spinal cord injury, motor neuron diseases, Alzheimer's disease and multiple sclerosis may benefit from increasing stem cell pool and promoting specific pathways of differentiation...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#11
Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov
BACKGROUND: Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28228489/age-dependent-shift-in-macrophage-polarisation-causes-inflammation-mediated-degeneration-of-enteric-nervous-system
#12
Laren Becker, Linh Nguyen, Jaspreet Gill, Subhash Kulkarni, Pankaj Jay Pasricha, Aida Habtezion
OBJECTIVE: The enteric nervous system (ENS) undergoes neuronal loss and degenerative changes with age. The cause of this neurodegeneration is poorly understood. Muscularis macrophages residing in close proximity to enteric ganglia maintain neuromuscular function via direct crosstalk with enteric neurons and have been implicated in the pathogenesis of GI motility disorders like gastroparesis and postoperative ileus. The aim of this study was to assess whether ageing causes alterations in macrophage phenotype that contributes to age-related degeneration of the ENS...
February 21, 2017: Gut
https://www.readbyqxmd.com/read/28227499/promotion-and-guidance-of-neural-network-formation-on-su-8-photoresist-microchannels-adjusted-with-multilayer-films
#13
Yung-Chiang Liu, I-Chi Lee, Kin-Fong Lei, Yung-Chiang Liu, I-Chi Lee, Kin-Fong Lei, Yung-Chiang Liu, I-Chi Lee, Kin-Fong Lei
Induction of neural stem/progenitor cells (NSPCs) and establishment of neural network are important issues on neural engineering. In this work, a platform was designed to control and evaluate the differentiation of NSPCs, neurite direction, and to promote the neurite outgrowth. Polyelectrolyte multilayer (PEM) films provide surface properties by and have been used to regulate NSPCs differentiation in our previous study. Herein, a culture platform composed of SU-8 microchannel and PEM films was designed to achieve the goal of promoting NSPCs differentiation and to evaluate the effect of PEM films on the guidance of neural network formation...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227435/gelatin-methacrylamide-hydrogel-with-graphene-nanoplatelets-for-neural-cell-laden-3d-bioprinting
#14
Wei Zhu, Brent T Harris, Lijie Grace Zhang, Wei Zhu, Brent T Harris, Lijie Grace Zhang, Wei Zhu, Brent T Harris, Lijie Grace Zhang
Nervous system is extremely complex which leads to rare regrowth of nerves once injury or disease occurs. Advanced 3D bioprinting strategy, which could simultaneously deposit biocompatible materials, cells and supporting components in a layer-by-layer manner, may be a promising solution to address neural damages. Here we presented a printable nano-bioink composed of gelatin methacrylamide (GelMA), neural stem cells, and bioactive graphene nanoplatelets to target nerve tissue regeneration in the assist of stereolithography based 3D bioprinting technique...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227432/colony-size-effect-on-neural-differentiation-of-embryonic-stem-cells-microprinted-on-stromal-cells
#15
Ramila Joshi, James Buchanan, Hossein Tavana, Ramila Joshi, James Buchanan, Hossein Tavana, Ramila Joshi, James Buchanan, Hossein Tavana
Controlling cellular microenvironment to induce neural differentiation of embryonic stem cells (ESCs) remains a major challenge. We address this need by introducing a micro-engineered co-culture system that resembles embryonic development in terms of direct intercellular interactions and induces neural differentiation of ESCs. A polymeric aqueous two-phase system (ATPS)-mediated robotic microprinting technology allows precise localization of mouse ESCs (mESCs) over a layer of supporting stromal cells. mESCs proliferate over a 2-week culture period into a single colony of defined size...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226539/directing-the-spatial-patterning-of-motor-neuron-differentiation-in-engineered-microenvironments
#16
Christopher J Demers, Greg Cox, Scott D Collins, Rosemary L Smith, Christopher J Demers, Greg Cox, Scott D Collins, Rosemary L Smith, Greg Cox, Christopher J Demers, Scott D Collins, Rosemary L Smith
Embryonic development of the spinal cord proceeds through a carefully orchestrated temporal and spatial sequence of chemical cues to provide precise patterning of adult cell types. Recreating this complex microenvironment in a standard cell culture dish is difficult, if not impossible. In this paper, a microfluidic device is used to recapitulate, in vitro, the graded patterning events which occur during early spinal cord development. The microdevice design is developed using COMSOL modeling, with which the spatiotemporal profiles of multiple, diffusible morphogens are simulated...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225193/human-neural-progenitor-transplantation-rescues-behavior-and-reduces-%C3%AE-synuclein-in-a-transgenic-model-of-dementia-with-lewy-bodies
#17
Natalie R S Goldberg, Samuel E Marsh, Joseph Ochaba, Brandon C Shelley, Hayk Davtyan, Leslie M Thompson, Joan S Steffan, Clive N Svendsen, Mathew Blurton-Jones
Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein α-synuclein (α-syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of α-syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB...
February 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28223921/epigenetic-modulation-of-stem-cells-in-neurodevelopment-the-role-of-methylation-and-acetylation
#18
REVIEW
Martyna Podobinska, Ilona Szablowska-Gadomska, Justyna Augustyniak, Ioanna Sandvig, Axel Sandvig, Leonora Buzanska
The coordinated development of the nervous system requires fidelity in the expression of specific genes determining the different neural cell phenotypes. Stem cell fate decisions during neurodevelopment are strictly correlated with their epigenetic status. The epigenetic regulatory processes, such as DNA methylation and histone modifications discussed in this review article, may impact both neural stem cell (NSC) self-renewal and differentiation and thus play an important role in neurodevelopment. At the same time, stem cell decisions regarding fate commitment and differentiation are highly dependent on the temporospatial expression of specific genes contingent on the developmental stage of the nervous system...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28223232/the-versatility-and-paradox-of-gdf-11
#19
REVIEW
A Jamaiyar, W Wan, D M Janota, M K Enrick, W M Chilian, L Yin
In addition to its roles in embryonic development, Growth and Differentiation Factor 11 (GDF 11) has recently drawn much interest about its roles in other processes, such as aging. GDF 11 has been shown to play pivotal roles in the rescue of the proliferative and regenerative capabilities of skeletal muscle, neural stem cells and cardiomyocytes. We would be remiss not to point that some controversy exists regarding the role of GDF 11 in biological processes and whether it will serve as a therapeutic agent. The latest studies have shown that the level of circulating GDF 11 correlates with the outcomes of patients with cardiovascular diseases, cancer and uremia...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28223217/pax3-inhibits-%C3%AE-tubulin-iii-expression-and-neuronal-differentiation-of-neural-stem-cell
#20
Sixian Cao, Jinfeng Du, Yan Lv, Hengrong Lin, Zuming Mao, Man Xu, Mei Liu, Yan Liu
PAX3 functions at the nodal point in neural stem cell maintenance and differentiation. Using bioinformatics methods, we identified PAX3 as a potential regulator of β-Tubulin-III (TUBB3) gene transcription, and the results indicated that PAX3 might be involved in neural stem cell (NSC) differentiation by orchestrating the expression of cytoskeletal proteins. In the present study, we reported that PAX3 could inhibit the differentiation of NSCs and the expression of TUBB3. Further, using luciferase and electrophoretic mobility shift assays, we demonstrated that PAX3 could bind to the promoter region of TUBB3 and inhibit TUBB3 transcription...
February 20, 2017: Biochemical and Biophysical Research Communications
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