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https://www.readbyqxmd.com/read/28083784/understanding-parkinson-s-disease-through-the-use-of-cell-reprogramming
#1
REVIEW
Rebecca Playne, Bronwen Connor
Recent progress in the field of somatic cell reprogramming offers exciting new possibilities for the study and treatment of Parkinson's disease (PD). Reprogramming technology offers the ability to untangle the diverse contributing risk factors for PD, such as ageing, genetics and environmental toxins. In order to gain novel insights into such a complex disease, cell-based models of PD should represent, as closely as possible, aged human dopaminergic neurons of the substantia nigra. However, the generation of high yields of functionally mature, authentic ventral midbrain dopamine (vmDA) neurons has not been easy to achieve...
January 12, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28075486/highly-expandable-human-ips-cell-derived-neural-progenitor-cells-npc-and-neurons-for-central-nervous-system-disease-modeling-and-high-throughput-screening
#2
Chialin Cheng, Daniel M Fass, Kat Folz-Donahue, Marcy E MacDonald, Stephen J Haggarty
Reprogramming of human somatic cells into induced pluripotent stem (iPS) cells has greatly expanded the set of research tools available to investigate the molecular and cellular mechanisms underlying central nervous system (CNS) disorders. Realizing the promise of iPS cell technology for the identification of novel therapeutic targets and for high-throughput drug screening requires implementation of methods for the large-scale production of defined CNS cell types. Here we describe a protocol for generating stable, highly expandable, iPS cell-derived CNS neural progenitor cells (NPC) using multi-dimensional fluorescence activated cell sorting (FACS) to purify NPC defined by cell surface markers...
January 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28075485/culturing-and-neuronal-differentiation-of-human-dental-pulp-stem-cells
#3
Sarita Goorha, Lawrence T Reiter
A major issue in studying human neurogenetic disorders, especially rare syndromes affecting the nervous system, is the ability to grow neuronal cultures that accurately represent these disorders for analysis. Although there has been some success in generating induced pluripotent stem (iPS) cells from both skin and blood, there are still limitations to the collection and production of iPS cells from these biospecimens. We have had significant success in collecting and growing human dental pulp stem (DPS) cells from exfoliated teeth sent to our laboratory by the parents of children with a variety of rare neurogenetic syndromes...
January 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28071834/molecular-profiling-of-human-ips-derived-hypothalamic-neurons-provides-developmental-insights-to-genetic-loci-for-body-weight-regulation
#4
Li Yao, Yuanhang Liu, Zhifang Qiu, Satish Kumar, Joanne E Curran, John Blangero, Yidong Chen, Donna M Lehman
BACKGROUND/OBJECTIVES: Recent data suggests that common genetic risk for metabolic disorders such as obesity may be human-specific and exert effects through the central nervous system. To overcome the limitation of human tissue access for study, we have generated induced human pluripotent stem cell (hiPSC)-derived neuronal cultures which recapture many features of hypothalamic neurons within the arcuate nucleus. Here we have comprehensively characterized this model across development, benchmarked these neurons to in vivo events, and demonstrate a link between obesity risk variants and hypothalamic development...
January 10, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28065649/translation-of-expanded-cgg-repeats-into-fmrpolyg-is-pathogenic-and-may-contribute-to-fragile-x-tremor-ataxia-syndrome
#5
Chantal Sellier, Ronald A M Buijsen, Fang He, Sam Natla, Laura Jung, Philippe Tropel, Angeline Gaucherot, Hugues Jacobs, Hamid Meziane, Alexandre Vincent, Marie-France Champy, Tania Sorg, Guillaume Pavlovic, Marie Wattenhofer-Donze, Marie-Christine Birling, Mustapha Oulad-Abdelghani, Pascal Eberling, Frank Ruffenach, Mathilde Joint, Mathieu Anheim, Veronica Martinez-Cerdeno, Flora Tassone, Rob Willemsen, Renate K Hukema, Stéphane Viville, Cecile Martinat, Peter K Todd, Nicolas Charlet-Berguerand
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a limited expansion of CGG repeats in the 5' UTR of FMR1. Two mechanisms are proposed to cause FXTAS: RNA gain-of-function, where CGG RNA sequesters specific proteins, and translation of CGG repeats into a polyglycine-containing protein, FMRpolyG. Here we developed transgenic mice expressing CGG repeat RNA with or without FMRpolyG. Expression of FMRpolyG is pathogenic, while the sole expression of CGG RNA is not...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28062005/gga-mir-2127-downregulates-the-translation-of-chicken-p53-and-attenuates-chp53-mediated-innate-immune-response-against-ibdv-infection
#6
Wei Ouyang, Yong-Shan Wang, Kai Meng, Qun-Xing Pan, Xiao-Li Wang, Xing-Xia Xia, Yu-Mei Zhu, Zhen-Wei Bi, Hai-Bin Zhang, Kai Luo
Infectious bursal disease (IBD) is characterized by the immune suppression of infected birds. The molecular mechanism by which IBD virus (IBDV) suppresses the host immune system remains to be elucidated. The tumor suppressor protein p53 can inhibit the replication of various viruses, but its effect on IBDV remains unknown. This study established an in vitro infection model based on DF-1 cells (chicken embryo fibroblast cell line) to investigate the antiviral effects of chicken p53 (chp53) on IBDV infection...
January 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28060316/an-alternative-and-validated-injection-method-for-accessing-the-subretinal-space-via-a-transcleral-posterior-approach
#7
Sachin Parikh, Andrew Le, Julian Davenport, Michael B Gorin, Steven Nusinowitz, Anna Matynia
Subretinal injections have been successfully used in both humans and rodents to deliver therapeutic interventions of proteins, viral agents, and cells to the interphotoreceptor/subretinal compartment that has direct exposure to photoreceptors and the retinal pigment epithelium (RPE). Subretinal injections of plasminogen as well as recent preclinical and clinical trials have demonstrated safety and/or efficacy of delivering viral vectors and stem cells to individuals with advanced retinal disease. Mouse models of retinal disease, particularly hereditary retinal dystrophies, are essential for testing these therapies...
December 7, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28059787/neurons-derived-from-induced-pluripotent-stem-cells-of-patients-with-down-syndrome-reproduce-early-stages-of-alzheimer-s-disease-type-pathology-in-vitro
#8
Erdem B Dashinimaev, Alexander S Artyuhov, Alexey P Bolshakov, Ekaterina A Vorotelyak, Andrey V Vasiliev
People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer's disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid-β (Aβ) manifested by increased secretion and accumulation of Aβ granules of Aβ42 pathological isoform with upregulated expression of the APP gene...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28057922/membrane-translocation-of-t-snare-protein-syntaxin-4-abrogates-ground-state-pluripotency-in-mouse-embryonic-stem-cells
#9
Natsumi Hagiwara-Chatani, Kota Shirai, Takumi Kido, Tomoatsu Horigome, Akihiro Yasue, Naoki Adachi, Yohei Hirai
Embryonic stem (ES) and induced pluripotent stem (iPS) cells are attractive tools for regenerative medicine therapies. However, aberrant cell populations that display flattened morphology and lose ground-state pluripotency often appear spontaneously, unless glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK1/2) are inactivated. Here, we show that membrane translocation of the t-SNARE protein syntaxin-4 possibly is involved in this phenomenon. We found that mouse ES cells cultured without GSK3β/MEK1/2 inhibitors (2i) spontaneously extrude syntaxin-4 at the cell surface and that artificial expression of cell surface syntaxin-4 induces appreciable morphological changes and mesodermal differentiation through dephosphorylation of Akt...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28051995/in-vitro-modelling-of-familial-amyloidotic-polyneuropathy-allows-quantitative-detection-of-transthyretin-amyloid-fibril-like-structures-in-hepatic-derivatives-of-patient-specific-induced-pluripotent-stem-cells
#10
Jeannine Hoepfner, Mandy Kleinsorge, Oliver Papp, Susanne Alfken, Robin Heiringhoff, Andreas Pich, Vanessa Sauer, Andree Zibert, Gudrun Göhring, Hartmut Schmidt, Malte Sgodda, Tobias Cantz
The transthyretin protein is thermodynamically destabilised by mutations in the transthyretin gene, promoting the formation of amyloid fibrils in various tissues. Consequently, impaired autonomic organ function is observed in patients suffering from transthyretin-related Familial Amyloidotic Polyneuropathy (FAP). The influence of individual genetic backgrounds on fibril formation as a potential cause of genotype-phenotype variations needs to be investigated in order to ensure efficient patient-specific therapies...
January 4, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28032018/a-multi-target-small-molecule-for-targeted-transcriptional-activation-of-therapeutically-significant-nervous-system-genes
#11
Yulei Wei, Ganesh N Pandian, Tingting Zou, Junichi Taniguchi, Shinsuke Sato, Gengo Kashiwazaki, Thangavel Vaijayanthi, Takuya Hidaka, Toshikazu Bando, Hiroshi Sugiyama
An integrated multi-target small molecule capable of altering dynamic epigenetic and transcription programs associated with the brain and nervous system has versatile applications in the regulation of therapeutic and cell-fate genes. Recently, we have been constructing targeted epigenetic ON switches by integrating sequence-specific DNA binding pyrrole-imidazole polyamides with a potent histone deacetylase inhibitor SAHA. Here, we identified a DNA-based epigenetic ON switch termed SAHA-L as the first-ever multi-target small molecule capable of inducing transcription programs associated with the human neural system and brain synapses networks in BJ human foreskin fibroblasts and 201B7-iPS cells...
December 2016: ChemistryOpen
https://www.readbyqxmd.com/read/28031331/activation-dependent-traf3-exon-8-alternative-splicing-is-controlled-by-celf2-and-hnrnp-c-binding-to-an-upstream-intronic-element
#12
Astrid-Solveig Schultz, Marco Preußner, Mario Bunse, Rotem Karni, Florian Heyd
Cell-type specific and inducible alternative splicing has a fundamental impact on regulating gene expression and cellular function in a variety of settings including activation and differentiation. We have recently shown that activation-induced skipping of TRAF3 exon 8 activates non-canonical NFkB signaling upon T cell stimulation, but the regulatory basis for this splicing event remains unknown. Here we identify cis- and trans-regulatory elements rendering this splicing switch activation-dependent and cell-type specific...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28024509/-effects-of-different-culture-systems-on-the-hematopoietic-differentiation-ability-of-ips-cells
#13
Di Fan, Wen-Yin He, Xiao-Hua Niu, Zhan-Hui Ou, Yu-Chang Chen, Xiao-Fang Sun
OBJECTIVE: To investigate the in vitro effects of different culture systems on hematopoietic differentiation ability of induced pluripotent stem (iPS) cells. METHOD: Two culture systems including E8 and mTESR(freeder-free medium), and the classical ES culture medium were chosen for culture of iPS cells. The iPS cells maintaining in above mentioning culcure systems were co-cultured with OP9 cells(murine bone marrow stromal cells) in vitro to be induced to differentiate into hematopoietic stem/progenitor cells...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28012798/generation-of-human-pluripotent-stem-cell-derived-hepatocyte-like-cells-for-drug-toxicity-screening
#14
REVIEW
Kazuo Takayama, Hiroyuki Mizuguchi
Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicity screening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicity screening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicity screening...
October 26, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28009813/translational-prospects-and-challenges-in-human-induced-pluripotent-stem-cell-research-in-drug-discovery
#15
REVIEW
Masaki Hosoya, Katherine Czysz
Despite continuous efforts to improve the process of drug discovery and development, achieving success at the clinical stage remains challenging because of a persistent translational gap between the preclinical and clinical settings. Under these circumstances, the discovery of human induced pluripotent stem (iPS) cells has brought new hope to the drug discovery field because they enable scientists to humanize a variety of pharmacological and toxicological models in vitro. The availability of human iPS cell-derived cells, particularly as an alternative for difficult-to-access tissues and organs, is increasing steadily; however, their use in the field of translational medicine remains challenging...
December 21, 2016: Cells
https://www.readbyqxmd.com/read/28009297/integrative-analysis-of-prkag2-cardiomyopathy-ips-and-microtissue-models-identifies-ampk-as-a-regulator-of-metabolism-survival-and-fibrosis
#16
J Travis Hinson, Anant Chopra, Andre Lowe, Calvin C Sheng, Rajat M Gupta, Rajarajan Kuppusamy, John O'Sullivan, Glenn Rowe, Hiroko Wakimoto, Joshua Gorham, Kehan Zhang, Kiran Musunuru, Robert E Gerszten, Sean M Wu, Christopher S Chen, Jonathan G Seidman, Christine E Seidman
AMP-activated protein kinase (AMPK) is a metabolic enzyme that can be activated by nutrient stress or genetic mutations. Missense mutations in the regulatory subunit, PRKAG2, activate AMPK and cause left ventricular hypertrophy, glycogen accumulation, and ventricular pre-excitation. Using human iPS cell models combined with three-dimensional cardiac microtissues, we show that activating PRKAG2 mutations increase microtissue twitch force by enhancing myocyte survival. Integrating RNA sequencing with metabolomics, PRKAG2 mutations that activate AMPK remodeled global metabolism by regulating RNA transcripts to favor glycogen storage and oxidative metabolism instead of glycolysis...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28009074/new-monoclonal-antibodies-to-defined-cell-surface-proteins-on-human-pluripotent-stem-cells
#17
Carmel M O'Brien, Hun S Chy, Qi Zhou, Shiri Blumenfeld, Jack W Lambshead, Xiaodong Liu, Joshua Kie, Bianca D Capaldo, Tung-Liang Chung, Timothy E Adams, Tram Phan, John D Bentley, William J Mckinstry, Karen Oliva, Paul J Mcmurrick, Yu-Chieh Wang, Fernando J Rossello, Geoffrey J Lindeman, Di Chen, Thierry Jarde, Amander T Clark, Helen E Abud, Jane E Visvader, Christian M Nefzger, Jose M Polo, Jeanne F Loring, Andrew L Laslett
The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterised monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures...
December 23, 2016: Stem Cells
https://www.readbyqxmd.com/read/28008721/therapy-of-primary-and-metastatic-liver-cancer-by-human-ips-cell-derived-myeloid-cells-producing-interferon-%C3%AE
#18
Masataka Sakisaka, Miwa Haruta, Yoshihiro Komohara, Satoshi Umemoto, Keiko Matsumura, Tokunori Ikeda, Motohiro Takeya, Yukihiro Inomata, Yasuharu Nishimura, Satoru Senju
BACKGROUND: iPS-ML are myeloid lineage cells with a proliferative capacity derived from induced pluripotent stem (iPS) cells. This study aimed to examine therapeutic effect of iPS-ML producing interferon-β (iPS-ML/IFN-β) towards primary and metastatic liver cancer and investigate the mechanism of that effect. METHODS: We established a xenograft model of liver metastasis by injecting the spleen of SCID mice with MKN-45 human gastric cancer cells and also a primary liver cancer model by injecting SK-HEP-1 human hepatocellular carcinoma cells into the liver...
December 23, 2016: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/28006781/allogeneic-compact-bone-derived-mesenchymal-stem-cell-transplantation-attenuates-the-severity-of-idiopathic-pneumonia-syndrome-in-a-murine-bone-marrow-transplantation-model
#19
Shu-Kai Qiao, Han-Yun Ren, Yong-Jin Shi, Wei Liu
BACKGROUND/AIMS: Idiopathic pneumonia syndrome (IPS) is a serious and life-threatening lung complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and currently no effective therapies exist. This study was designed to determine whether transplantation of allogeneic murine compact bone derived- mesenchymal stem cells (CB-MSCs) could prevent the development of IPS. METHODS: We tested the effects of CB-MSCs transplantation on IPS using an established murine model of C57BL/6 (H-2b)→BALB/c (H-2d)...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28000155/hepatocyte-nuclear-factor-4-alpha-promotes-definitive-endoderm-differentiation-from-human-induced-pluripotent-stem-cells
#20
Morifumi Hanawa, Kazuo Takayama, Fuminori Sakurai, Masashi Tachibana, Hiroyuki Mizuguchi
Hepatocyte nuclear factor 4 alpha (HNF4α) is a key transcription factor for liver development. Although HNF4α is necessary for hepatoblast differentiation, the function of HNF4α before the hepatoblast differentiation, such as in definitive endoderm differentiation, is not well known. In addition, it is known that there are nine HNF4α isoforms, but the expression and function of each HNF4α isoform during the definitive endoderm differentiation is also not clear. In this study, we examined the expression pattern of HNF4α and its functions in the definitive endoderm differentiation from human induced pluripotent stem (iPS) cells...
December 21, 2016: Stem Cell Reviews
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