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Induced pluripotent cells

Madeline Williams, Smrithi Prem, Xiaofeng Zhou, Paul Matteson, Percy Luk Yeung, Chi-Wei Lu, Zhiping Pang, Linda Brzustowicz, James H Millonig, Emanuel Dicicco-Bloom
Human brain development proceeds through a series of precisely orchestrated processes, with earlier stages distinguished by proliferation, migration, and neurite outgrowth; and later stages characterized by axon/dendrite outgrowth and synapse formation. In neurodevelopmental disorders, often one or more of these processes are disrupted, leading to abnormalities in brain formation and function. With the advent of human induced pluripotent stem cell (hiPSC) technology, researchers now have an abundant supply of human cells that can be differentiated into virtually any cell type, including neurons...
March 2, 2018: Journal of Visualized Experiments: JoVE
Rinat Sultanov, Olga Lebedeva, Georgij Arapidi, Maria Lagarkova, Sergei Kiselev
The genetic reprogramming technology allows generation of induced pluripotent stem cells (iPSCs) from somatic cells (Takahashi and Yamanaka, 2006) [1]. iPSCs have the ability to self-renew, and to differentiate into any type of somatic cells, and are considered as a promising tool for drug development, disease modeling, and regenerative medicine. The reprogramming factors (oct4, sox2, klf4, c-myc) can be delivered to the cell nucleus either by vectors integrating into the genome (lentiviruses, retroviruses) or by non-integrative methods (e...
April 2018: Data in Brief
Paola Spitalieri, Rosa V Talarico, Silvia Caioli, Michela Murdocca, Annalucia Serafino, Marco Girasole, Simone Dinarelli, Giovanni Longo, Sabina Pucci, Annalisa Botta, Giuseppe Novelli, Cristina Zona, Ruggiero Mango, Federica Sangiuolo
Myotonic Dystrophy type 1 (DM1) is a multisystemic disease, autosomal dominant, caused by a CTG repeat expansion in DMPK gene. We assessed the appropriateness of patient-specific induced pluripotent stem cell-derived cardiomyocytes (CMs) as a model to recapitulate some aspects of the pathogenetic mechanism involving cardiac manifestations in DM1 patients. Once obtained in vitro, CMs have been characterized for their morphology and their functionality. CMs DM1 show intranuclear foci and transcript markers abnormally spliced respect to WT ones, as well as several irregularities in nuclear morphology, probably caused by an unbalanced lamin A/C ratio...
March 15, 2018: Journal of Molecular and Cellular Cardiology
Caleb Pitcairn, Willayat Yousuf Wani, Joseph R Mazzulli
The finding that mutations in the Gaucher's Disease (GD) gene GBA1 are a strong risk factor for Parkinson's Disease (PD) has allowed for unique insights into pathophysiology centered on disruption of the autophagic-lysosomal pathway. Protein aggregations in the form of Lewy bodies and the effects of canonical PD mutations that converge on the lysosomal degradation system suggest that neurodegeneration in PD is mediated by dysregulation of protein homeostasis. The well-characterized clinical and pathological relationship between PD and the lysosomal storage disorder GD emphasizes the importance of dysregulated protein metabolism in neurodegeneration, and one intriguing piece of this relationship is a shared phenotype of autophagic-lysosomal dysfunction in both diseases...
March 14, 2018: Neurobiology of Disease
Masataka Nishiga, Hongchao Guo, Joseph C Wu
No abstract text is available yet for this article.
March 13, 2018: European Heart Journal
Gualtiero Alvisi, Marta Trevisan, Giulia Masi, Vanessa Canel, Luciana Caenazzo, Patrizia Nespeca, Luisa Barzon, Enzo Di Iorio, Vanessa Barbaro, Giorgio Palù
Human oral mucosa epithelial stem cells (hOMESCs) were obtained from a fresh oral biopsy collected from a healthy subject at the Fondazione Banca degli Occhi del Veneto (FBOV). An integration-free reprogramming protocol was applied exploiting episomal plasmids transfected into cells using a Nucleofector device. Around day 20 post transfection, several human induced pluripotent stem cell (hiPSC) colonies were manually picked and expanded. One of these (UNIPDi001-A-hiPSCs) expressed undifferentiated state marker alkaline phosphatase along with a panel of pluripotency state markers and was able to differentiate into the derivatives of all the three germ layers...
February 18, 2018: Stem Cell Research
Peter Stacey, Anne Mai Wassermann, Laura Kammonen, Emma Impey, Anna Wilbrey, Darren Cawkill
Screening against a disease-relevant phenotype to identify compounds that change the outcome of biological pathways, rather than just the activity of specific targets, offers an alternative approach to find modulators of disease characteristics. However, in pain research, use of in vitro phenotypic screens has been impeded by the challenge of sourcing relevant neuronal cell types in sufficient quantity and developing functional end-point measurements with a direct disease link. To overcome these hurdles, we have generated human induced pluripotent stem cell (hiPSC)-derived sensory neurons at a robust production scale using the concept of cryopreserved "near-assay-ready" cells to decouple complex cell production from assay development and screening...
March 1, 2018: SLAS Discovery
Sa Cai, Daisy K Y Shum, Ying-Shing Chan
Here we describe the in vitro derivation of sensory neurons for use in effecting fate commitment of Schwann cell-like cells derived from human bone marrow stromal cells (hBMSCs). We adopt a novel combination of small molecules in an 8-day program that induces the differentiation of human induced pluripotent stem cells into sensory neurons. In co-cultures, the derived sensory neurons present contact-dependent cues to direct hBMSC-derived Schwann cell-like cells toward the Schwann cell fate. These derived human Schwann cells survive passaging and cryopreservation, retain marker expression despite withdrawal of glia-inducing medium and neuronal cues, demonstrate capacity for myelination, and therefore promise application in autologous transplantation and re-myelination therapy...
2018: Methods in Molecular Biology
Zhiyi Qin, Peter Stoilov, Xuegong Zhang, Yi Xing
Alternative first exons diversify the transcriptomes of eukaryotes by producing variants of the 5' Untranslated Regions (5'UTRs) and N-terminal coding sequences. Accurate transcriptome-wide detection of alternative first exons typically requires specialized experimental approaches that are designed to identify the 5' ends of transcripts. We developed a computational pipeline SEASTAR that identifies first exons from RNA-seq data alone then quantifies and compares alternative first exon usage across multiple biological conditions...
March 13, 2018: Nucleic Acids Research
Junya Kitadani, Toshiyasu Ojima, Hiromitsu Iwamoto, Hirotaka Tabata, Mikihito Nakamori, Masaki Nakamura, Keiji Hayata, Masahiro Katsuda, Masayasu Miyajima, Hiroki Yamaue
Clinical application of dendritic cell (DC) vaccine therapy is hindered by the need for a large quantity of DCs generated from peripheral blood monocytes of the patient. We investigated whether genetically modified human induced pluripotent stem cell (iPSC)-derived dendritic cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce CEA-specific cytotoxic T cells in a human model and whether genetically modified mouse iPSDCs (miPSDCs) expressing CEA showed an actual antitumor effect using a CEA transgenic mouse model...
March 15, 2018: Scientific Reports
Suet Nee Chen, Matthew R G Taylor, Luisa Mestroni
No abstract text is available yet for this article.
March 2018: Circ Genom Precis Med
Ibrahim El-Battrawy, Zhihan Zhao, Huan Lan, Xin Li, Gökhan Yücel, Siegfried Lang, Katherine Sattler, Jan-Dierk Schünemann, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Thomas Wieland, Karen Bieback, Ralf Bauer, Antonius Ratte, Regina Pribe-Wolferts, Kleopatra Rapti, Daniel Nowak, Janina Wittig, Dierk Thomas, Patrick Most, Hugo A Katus, Ursula Ravens, Constanze Schmidt, Martin Borggrefe, Xiao-Bo Zhou, Oliver J Müller, Ibrahim Akin
BACKGROUND: Limb-Girdle muscular dystrophies (LGMD) are a heritable group of genetically determined disorders with a primary involvement of the pelvic or shoulder girdle musculature with partially cardiac manifestation, such as dilated cardiomyopathy (DCM) and life-threatening tachyarrhythmia. We report here that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes from a patient with LGMD2I and DCM associated with recurrent ventricular tachycardia displayed ion channel dysfunction and abnormality of calcium homeostasis...
March 2018: Circ Genom Precis Med
Emily P Dawson, Denise G Lanza, Nicholas J Webster, Susan M Benton, Isao Suetake, Jason D Heaney
Testicular teratomas result from anomalies in embryonic germ cell development. In 129 inbred mice, teratoma initiation coincides with germ cell sex-specific differentiation and the mitotic-meiotic switch: XX and XY germ cells repress pluripotency, XX germ cells initiate meiosis, and XY germ cells activate male-specific differentiation and mitotic arrest. Here, we report that expression of Nanos2 , a gene that is crucial to male sex specification, is delayed in teratoma-susceptible germ cells. Decreased expression of Nanos2 was found to be due, in part, to the Nanos2 allele present in 129 mice...
March 15, 2018: Development
Meixiang Zhang, Justine Ngo, Filomena Pirozzi, Ying-Pu Sun, Anthony Wynshaw-Boris
BACKGROUND: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages...
March 15, 2018: Stem Cell Research & Therapy
Alexandra J Harvey, Carmel O'Brien, Jack Lambshead, John R Sheedy, Joy Rathjen, Andrew L Laslett, David K Gardner
Reprogramming somatic cells to a pluripotent cell state (induced Pluripotent Stem (iPS) cells) requires reprogramming of metabolism to support cell proliferation and pluripotency, most notably changes in carbohydrate turnover that reflect a shift from oxidative to glycolytic metabolism. Some aspects of iPS cell metabolism differ from embryonic stem (ES) cells, which may reflect a parental cell memory, or be a consequence of the reprogramming process. In this study, we compared the metabolism of 3 human iPS cell lines to assess the fidelity of metabolic reprogramming...
2018: PloS One
Plansky Hoang, Jason Wang, Bruce R Conklin, Kevin E Healy, Zhen Ma
The creation of human induced pluripotent stem cells (hiPSCs) has provided an unprecedented opportunity to study tissue morphogenesis and organ development through 'organogenesis-in-a-dish'. Current approaches to cardiac organoid engineering rely on either direct cardiac differentiation from embryoid bodies (EBs) or generation of aligned cardiac tissues from predifferentiated cardiomyocytes from monolayer hiPSCs. To experimentally model early cardiac organogenesis in vitro, our protocol combines biomaterials-based cell patterning with stem cell organoid engineering...
April 2018: Nature Protocols
Tingchao Mao, Chengquan Han, Ruizhi Deng, Biao Wei, Peng Meng, Yan Luo, Yong Zhang
Epigenetic modifications extensively occur in mammalian embryonic development and cell differentiation process. They play an essential role in the reprogramming of nuclei during somatic cell nuclear transfer (SCNT) and subsequent in vitro embryonic development. Recently, SCNT embryos have been verified to contain a subnormal level of histone H3K4 dimethylation (H3K4me2) in contrast to in vitro fertilized embryos. This finding suggested that increasing H3K4me2 levels may ameliorate the aberrant development of cloned embryos...
March 15, 2018: Systems Biology in Reproductive Medicine
Aleta Pupovac, Berna Senturk, Chiara Griffoni, Katharina Maniura-Weber, Markus Rottmar, Sally L McArthur
3D human skin models provide a platform for toxicity testing, biomaterials evaluation, and investigation of fundamental biological processes. However, the majority of current in vitro models lack an inflammatory system, vasculature, and other characteristics of native skin, indicating scope for more physiologically complex models. Looking at the immune system, there are a variety of cells that could be integrated to create novel skin models, but to do this effectively it is also necessary to understand the interface between skin biology and tissue engineering as well as the different roles the immune system plays in specific health and disease states...
March 15, 2018: Advanced Healthcare Materials
Alan D Marmorstein, Adiv A Johnson, Lori A Bachman, Cynthia Andrews-Pfannkoch, Travis Knudsen, Benjamin J Gilles, Matthew Hill, Jarel K Gandhi, Lihua Y Marmorstein, Jose S Pulido
Autosomal recessive bestrophinopathy (ARB) is caused by mutations in the gene BEST1 which encodes bestrophin 1 (Best1), an anion channel expressed in retinal pigment epithelial (RPE) cells. It has been hypothesized that ARB represents the human null phenotype for BEST1 and that this occurs due to nonsense mediated decay (NMD). To test this hypothesis, we generated induced pluripotent stem cells (iPSCs) from a patient with ARB and her parents. After differentiation to retinal pigment epithelial (iPSC-RPE) cells, both BEST1 mRNA and Best1 protein expression were compared to controls...
March 14, 2018: Scientific Reports
Yingqian Peng, Edouard Baulier, Yifeng Ke, Alejandra Young, Novruz B Ahmedli, Steven D Schwartz, Debora B Farber
Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions...
2018: PloS One
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