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https://www.readbyqxmd.com/read/28092083/role-of-dopamine-d2-d3-receptors-in-development-plasticity-and-neuroprotection-in-human-ipsc-derived-midbrain-dopaminergic-neurons
#1
Federica Bono, Paola Savoia, Adele Guglielmi, Massimo Gennarelli, Giovanna Piovani, Sandra Sigala, Damiana Leo, Stefano Espinoza, Raul R Gainetdinov, Paola Devoto, PierFranco Spano, Cristina Missale, Chiara Fiorentini
The role of dopamine D2 and D3 receptors (D2R/D3R), located on midbrain dopaminergic (DA) neurons, in the regulation of DA synthesis and release and in DA neuron homeostasis has been extensively investigated in rodent animal models. By contrast, the properties of D2R/D3R in human DA neurons have not been elucidated yet. On this line, the use of human-induced pluripotent stem cells (hiPSCs) for producing any types of cells has offered the innovative opportunity for investigating the human neuronal phenotypes at the molecular levels...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28089995/systematic-evaluation-of-markers-used-for-the-identification-of-human-induced-pluripotent-stem-cells
#2
Sumitha Prameela Bharathan, Kannan Vrindavan Manian, Syed Mohammed Musheer Aalam, Dhavapriya Palani, Prashant Ajit Deshpande, Mankuzhy Damodaran Pratheesh, Alok Srivastava, Shaji Ramachandran Velayudhan
Low efficiency of somatic cell reprogramming and heterogeneity among human induced pluripotent stem cells (hiPSCs) demand extensive characterization of isolated clones before their use in downstream applications. By monitoring human fibroblasts undergoing reprogramming for their morphological changes and expression of fibroblast (CD13), pluripotency markers (SSEA-4 and TRA-1-60) and a retrovirally expressed red fluorescent protein (RV-RFP), we compared the efficiency of these features to identify bona fide hiPSC colonies...
January 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28089908/human-aml-ipscs-reacquire-leukemic-properties-after-differentiation-and-model-clonal-variation-of-disease
#3
Mark P Chao, Andrew J Gentles, Susmita Chatterjee, Feng Lan, Andreas Reinisch, M Ryan Corces, Seethu Xavy, Jinfeng Shen, Daniel Haag, Soham Chanda, Rahul Sinha, Rachel M Morganti, Toshinobu Nishimura, Mohamed Ameen, Haodi Wu, Marius Wernig, Joseph C Wu, Ravindra Majeti
Understanding the relative contributions of genetic and epigenetic abnormalities to acute myeloid leukemia (AML) should assist integrated design of targeted therapies. In this study, we generated induced pluripotent stem cells (iPSCs) from AML patient samples harboring MLL rearrangements and found that they retained leukemic mutations but reset leukemic DNA methylation/gene expression patterns. AML-iPSCs lacked leukemic potential, but when differentiated into hematopoietic cells, they reacquired the ability to give rise to leukemia in vivo and reestablished leukemic DNA methylation/gene expression patterns, including an aberrant MLL signature...
December 26, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28079893/mitochondrial-respiratory-dysfunction-disturbs-neuronal-and-cardiac-lineage-commitment-of-human-ipscs
#4
Mutsumi Yokota, Hideyuki Hatakeyama, Yasuha Ono, Miyuki Kanazawa, Yu-Ichi Goto
Mitochondrial diseases are genetically heterogeneous and present a broad clinical spectrum among patients; in most cases, genetic determinants of mitochondrial diseases are heteroplasmic mitochondrial DNA (mtDNA) mutations. However, it is uncertain whether and how heteroplasmic mtDNA mutations affect particular cellular fate-determination processes, which are closely associated with the cell-type-specific pathophysiology of mitochondrial diseases. In this study, we established two isogenic induced pluripotent stem cell (iPSC) lines each carrying different proportions of a heteroplasmic m...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28076757/ipsc-derived-retina-transplants-improve-vision-in-rd1-end-stage-retinal-degeneration-mice
#5
Michiko Mandai, Momo Fujii, Tomoyo Hashiguchi, Genshiro A Sunagawa, Shinichiro Ito, Jianan Sun, Jun Kaneko, Junki Sho, Chikako Yamada, Masayo Takahashi
Recent success in functional recovery by photoreceptor precursor transplantation in dysfunctional retina has led to an increased interest in using embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal progenitors to treat retinal degeneration. However, cell-based therapies for end-stage degenerative retinas that have lost the outer nuclear layer (ONL) are still a big challenge. In the present study, by transplanting mouse iPSC-derived retinal tissue (miPSC retina) in the end-stage retinal-degeneration model (rd1), we visualized the direct contact between host bipolar cell terminals and the presynaptic terminal of graft photoreceptors by gene labeling, showed light-responsive behaviors in transplanted rd1 mice, and recorded responses from the host retina with transplants by ex vivo micro-electroretinography and ganglion cell recordings using a multiple-electrode array system...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28073160/activation-of-jnk-pathway-aggravates-proteotoxicity-of-hepatic-mutant-z-alpha1-antitrypsin
#6
Nunzia Pastore, Sergio Attanasio, Barbara Granese, Jeffrey Teckman, Andrew A Wilson, Andrea Ballabio, And Nicola Brunetti-Pierri
Alpha1-antitrypsin deficiency is a genetic disease that can affect both the lung and the liver. The vast majority of patients harbor a mutation in the SERPINA1 gene resulting in a single amino acid substitution that results in an unfolded protein that is prone to polymerization. Therefore, the liver disease is caused by a gain of function mechanism due to accumulation of the mutant Z alpha1-antitrypsin (ATZ) and is a key example of an important disease mechanism induced by protein toxicity. Intracellular retention of ATZ triggers a complex injury cascade including apoptosis and other mechanisms, although several aspects of the disease pathogenesis are still unclear...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28073086/human-neural-progenitors-derived-from-integration-free-ipscs-for-sci-therapy
#7
Ying Liu, Yiyan Zheng, Shenglan Li, Haipeng Xue, Karl Schmitt, Georgene W Hergenroeder, Jiaqian Wu, Yuanyuan Zhang, Dong H Kim, Qilin Cao
As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28069827/melatonin-mediated-upregulation-of-glut1-blocks-exit-from-pluripotency-by-increasing-the-uptake-of-oxidized-vitamin-c-in-mouse-embryonic-stem-cells
#8
Haibo Wu, Chao Song, Jingcheng Zhang, Jiamin Zhao, Beibei Fu, Tingchao Mao, Yong Zhang
Melatonin and vitamin C are powerful antioxidants that improve the reprogramming efficiency of induced pluripotent stem cells (iPSCs). However, the effects of the combined treatment of vitamin C and melatonin on the differentiation of embryonic stem cells (ESCs) have not yet been examined. In this study, we showed that melatonin synergizes with vitamin C to derail exit from pluripotency of mouse ESCs. This effect is related to the increased uptake of dehydroascorbate, the oxidized form of vitamin C, through glucose transporter 1 (Glut1) transporter, which in turn, is upregulated by melatonin treatment...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069694/myocardial-tissue-engineering-with-cells-derived-from-human-induced-pluripotent-stem-cells-and-a-native-like-high-resolution-3-dimensionally-printed-scaffold
#9
Ling Gao, Molly Kupfer, Jangwook Jung, Libang Yang, Patrick Zhang, Yong Sie, Quyen Tran, Visar Ajeti, Brian Freeman, Vladimir Fast, Paul Campagnola, Brenda Ogle, Jianyi Zhang
RATIONALE: Conventional three-dimensional (3D) printing techniques cannot produce structures of the size at which individual cells interact. OBJECTIVE: Here, we used multiphoton-excited, 3-dimensional printing (MPE-3DP) to generate a native-like, extracellular matrix (ECM) scaffold with submicron resolution, and then seeded the scaffold with cardiomyocytes (CMs), smooth-muscle cells (SMCs), and endothelial cells (ECs) that had been differentiated from human induced-pluripotent stem cells (iPSCs) to generate a human, iPSC-derived cardiac muscle patch (hCMP), which was subsequently evaluated in a murine model of myocardial infarction (MI)...
January 9, 2017: Circulation Research
https://www.readbyqxmd.com/read/28065643/ctip-specific-roles-during-cell-reprogramming-have-long-term-consequences-in-the-survival-and-fitness-of-induced-pluripotent-stem-cells
#10
Daniel Gómez-Cabello, Cintia Checa-Rodríguez, María Abad, Manuel Serrano, Pablo Huertas
Acquired genomic instability is one of the major concerns for the clinical use of induced pluripotent stem cells (iPSCs). All reprogramming methods are accompanied by the induction of DNA damage, of which double-strand breaks are the most cytotoxic and mutagenic. Consequently, DNA repair genes seem to be relevant for accurate reprogramming to minimize the impact of such DNA damage. Here, we reveal that reprogramming is associated with high levels of DNA end resection, a critical step in homologous recombination...
December 27, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/28062362/induced-pluripotent-stem-cell-technology-a-window-for-studying-the-pathogenesis-of-acquired-aplastic-anemia-and-possible-applications
#11
REVIEW
Mahmoud Elbadry, J Luis Espinoza, Shinji Nakao
Recent progress in human induced pluripotent stem cells (iPSCs) has opened the door to better understand the biology of human diseases, especially in rare disorders, such as acquired aplastic anemia (AA), in which the target hematopoietic tissues are depleted. The advent of somatic cell reprogramming has presented new routes for generating hematopoietic stem cells (HSCs) from patient-derived iPSCs and their differentiation into hematopoietic lineages. The purpose of this review is to discuss the recent advances in iPSC research technology and its potential applications in disease modeling for understanding the pathogenesis of bone marrow failure syndrome (BMFS) and the potential clinical utility of iPSC-derived cells...
January 3, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28060310/induced-pluripotent-stem-cell-generation-from-blood-cells-using-sendai-virus-and-centrifugation
#12
Yeri Alice Rim, Yoojun Nam, Ji Hyeon Ju
The recent development of human induced pluripotent stem cells (hiPSCs) proved that mature somatic cells can return to an undifferentiated, pluripotent state. Now, reprogramming is done with various types of adult somatic cells: keratinocytes, urine cells, fibroblasts, etc. Early experiments were usually done with dermal fibroblasts. However, this required an invasive surgical procedure to obtain fibroblasts from the patients. Therefore, suspension cells, such as blood and urine cells, were considered ideal for reprogramming because of the convenience of obtaining the primary cells...
December 21, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057917/an-integrated-miniature-bioprocessing-for-personalized-human-induced-pluripotent-stem-cell-expansion-and-differentiation-into-neural-stem-cells
#13
Haishuang Lin, Qiang Li, Yuguo Lei
Human induced pluripotent stem cells (iPSCs) are ideal cell sources for personalized cell therapies since they can be expanded to generate large numbers of cells and differentiated into presumably all the cell types of the human body in vitro. In addition, patient specific iPSC-derived cells induce minimal or no immune response in vivo. However, with current cell culture technologies and bioprocessing, the cost for biomanufacturing clinical-grade patient specific iPSCs and their derivatives are very high and not affordable for majority of patients...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28057485/efficient-induction-of-dopaminergic-neuron-differentiation-from-induced-pluripotent-stem-cells-reveals-impaired-mitophagy-in-park2-neurons
#14
Sadafumi Suzuki, Wado Akamatsu, Fumihiko Kisa, Takefumi Sone, Kei-Ichi Ishikawa, Naoko Kuzumaki, Hiroyuki Katayama, Atsushi Miyawaki, Nobutaka Hattori, Hideyuki Okano
Patient-specific induced pluripotent stem cells (iPSCs) show promise for use as tools for in vitro modeling of Parkinson's disease. We sought to improve the efficiency of dopaminergic (DA) neuron induction from iPSCs by the using surface markers expressed in DA progenitors to increase the significance of the phenotypic analysis. By sorting for a CD184(high)/CD44(-) fraction during neural differentiation, we obtained a population of cells that were enriched in DA neuron precursor cells and achieved higher differentiation efficiencies than those obtained through the same protocol without sorting...
January 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28057064/the-lncrnas-involved-in-mouse-airway-allergic-inflammation-following-induced-pluripotent-stem-cell-mesenchymal-stem-cell-treatment
#15
Shu-Yue Wang, Xing-Liang Fan, Qiu-Ning Yu, Meng-Xia Deng, Yue-Qi Sun, Wen-Xiang Gao, Cheng-Lin Li, Jian-Bo Shi, Qing-Ling Fu
BACKGROUND: We have previously reported that induced pluripotent stem cell (iPSC)-mesenchymal stem cells (MSCs) alleviated asthma inflammation in mice. Long noncoding RNAs (lncRNAs) were recently reported as being involved in the immune responses. However, whether lncRNAs are associated with iPSC-MSC immunomodulation in allergic inflammation is still unclear. METHODS: Mice were induced into an asthmatic state and received treatment consisting of iPSC-MSCs. Memory T cells isolated from sensitized mice were challenged and co-cultured with iPSC-MSCs in vitro...
January 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28054918/app-modulates-kcc2-expression-and-function-in-hippocampal-gabaergic-inhibition
#16
Ming Chen, Jinzhao Wang, Jinxiang Jiang, Xingzhi Zheng, Nicholas J Justice, Kun Wang, Xiangqian Ran, Yi Li, Qingwei Huo, Jiajia Zhang, Hongmei Li, Nannan Lu, Ying Wang, Hui Zheng, Cheng Long, Li Yang
Amyloid precursor protein (APP) is enriched at the synapse, but its synaptic function is still poorly understood. We previously showed that GABAergic short-term plasticity is impaired in App knock-out (App(-/-)) animals, but the precise mechanism by which APP regulates GABAergic synaptic transmission has remained elusive. Using electrophysiological, biochemical, moleculobiological, and pharmacological analysis, here we show that APP can physically interact with KCC2, a neuron-specific K(+)-Cl(-) cotransporter that is essential for Cl(-) homeostasis and fast GABAergic inhibition...
January 5, 2017: ELife
https://www.readbyqxmd.com/read/28054653/the-long-non-coding-rna-neat1-is-responsive-to-neuronal-activity-and-is-associated-with-hyperexcitability-states
#17
Guy Barry, James A Briggs, Do Won Hwang, Sam P Nayler, Patrick R J Fortuna, Nicky Jonkhout, Fabien Dachet, Jesper L V Maag, Pieter Mestdagh, Erin M Singh, Lotta Avesson, Dominik C Kaczorowski, Ezgi Ozturk, Nigel C Jones, Irina Vetter, Luis Arriola-Martinez, Jianfei Hu, Gloria R Franco, Victoria M Warn, Andrew Gong, Marcel E Dinger, Frank Rigo, Leonard Lipovich, Margaret J Morris, Terence J O'Brien, Dong Soo Lee, Jeffrey A Loeb, Seth Blackshaw, John S Mattick, Ernst J Wolvetang
Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that the long non-coding RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 is dynamically regulated by neuronal activity in vitro and in vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 and KCNIP1, and induces a neuronal hyper-potentiation phenotype in iPSC-derived human cortical neurons following antisense oligonucleotide knockdown...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052261/cochlear-cell-modeling-using-disease-specific-ipscs-unveils-a-degenerative-phenotype-and-suggests-treatments-for-congenital-progressive-hearing-loss
#18
Makoto Hosoya, Masato Fujioka, Takefumi Sone, Satoshi Okamoto, Wado Akamatsu, Hideki Ukai, Hiroki R Ueda, Kaoru Ogawa, Tatsuo Matsunaga, Hideyuki Okano
Hearing impairments are the most common symptom of congenital defects, and they generally remain intractable to treatment. Pendred syndrome, the most frequent syndromic form of hereditary hearing loss, is associated with mutations in the anion exchanger pendrin. Loss of pendrin function as an anion exchanger is thought to be causative, but rodent models do not exhibit progressive deafness. Here, we report a degenerative phenotype exhibiting mutant pendrin aggregates and increased susceptibility to cellular stresses in cochlear epithelial cells induced from patient-derived induced pluripotent stem cells (iPSCs)...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28052243/networks-of-cultured-ipsc-derived-neurons-reveal-the-human-synaptic-activity-regulated-adaptive-gene-program
#19
Priit Pruunsild, C Peter Bengtson, Hilmar Bading
Long-term adaptive responses in the brain, such as learning and memory, require synaptic activity-regulated gene expression, which has been thoroughly investigated in rodents. Using human iPSC-derived neuronal networks, we show that the human and the mouse synaptic activity-induced transcriptional programs share many genes and both require Ca(2+)-regulated synapse-to-nucleus signaling. Species-specific differences include the noncoding RNA genes BRE-AS1 and LINC00473 and the protein-coding gene ZNF331, which are absent in the mouse genome, as well as several human genes whose orthologs are either not induced by activity or are induced with different kinetics in mice...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28050713/metabolic-profiling-of-human-long-term-liver-models-and-hepatic-clearance-predictions-from-in-vitro-data-using-nonlinear-mixed-effects-modeling
#20
Nicole A Kratochwil, Christophe Meille, Stephen Fowler, Florian Klammers, Aynur Ekiciler, Birgit Molitor, Sandrine Simon, Isabelle Walter, Claudia McGinnis, Johanna Walther, Brian Leonard, Miriam Triyatni, Hassan Javanbakht, Christoph Funk, Franz Schuler, Thierry Lavé, Neil J Parrott
Early prediction of human clearance is often challenging, in particular for the growing number of low-clearance compounds. Long-term in vitro models have been developed which enable sophisticated hepatic drug disposition studies and improved clearance predictions. Here, the cell line HepG2, iPSC-derived hepatocytes (iCell®), the hepatic stem cell line HepaRG™, and human hepatocyte co-cultures (HμREL™ and HepatoPac®) were compared to primary hepatocyte suspension cultures with respect to their key metabolic activities...
January 3, 2017: AAPS Journal
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