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https://www.readbyqxmd.com/read/27912091/genetic-ablation-of-axl-does-not-protect-human-neural-progenitor-cells-and-cerebral-organoids-from-zika-virus-infection
#1
Michael F Wells, Max R Salick, Ole Wiskow, Daniel J Ho, Kathleen A Worringer, Robert J Ihry, Sravya Kommineni, Bilada Bilican, Joseph R Klim, Ellen J Hill, Liam T Kane, Chaoyang Ye, Ajamete Kaykas, Kevin Eggan
Zika virus (ZIKV) can cross the placental barrier, resulting in infection of the fetal brain and neurological defects including microcephaly. The cellular tropism of ZIKV and the identity of attachment factors used by the virus to gain access to key cell types involved in pathogenesis are under intense investigation. Initial studies suggested that ZIKV preferentially targets neural progenitor cells (NPCs), providing an explanation for the developmental phenotypes observed in some pregnancies. The AXL protein has been nominated as a key attachment factor for ZIKV in several cell types including NPCs...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27911758/multimodal-imaging-for-dreadd-expressing-neurons-in-living-brain-and-their-application-to-implantation-of-ipsc-derived-neural-progenitors
#2
Bin Ji, Hiroyuki Kaneko, Takafumi Minamimoto, Haruhisa Inoue, Hiroki Takeuchi, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Chie Seki, Maiko Ono, Masaki Tokunaga, Satoshi Tsukamoto, Koji Tanabe, Ryong-Moon Shin, Takeharu Minamihisamatsu, Seiji Kito, Barry J Richmond, Tetsuya Suhara, Makoto Higuchi
: Chemogenetic manipulation of neuronal activities has been enabled by a designer receptor (designer receptor exclusively activated by designer drugs, DREADD) that is activated exclusively by clozapine-N-oxide (CNO). Here, we applied CNO as a functional reporter probe to positron emission tomography (PET) of DREADD in living brains. Mutant human M4 DREADD (hM4Di) expressed in transgenic (Tg) mouse neurons was visualized by PET with microdose [(11)C]CNO. Deactivation of DREADD-expressing neurons in these mice by nonradioactive CNO at a pharmacological dose could also be captured by arterial spin labeling MRI (ASL-MRI)...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911371/development-of-stem-cell-derived-antigen-specific-regulatory-t-cells-against-autoimmunity
#3
Mohammad Haque, Kristin Fino, Praneet Sandhu, Jianxun Song
Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4(+) T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911363/generation-of-induced-pluripotent-stem-cells-from-human-melanoma-tumor-infiltrating-lymphocytes
#4
Hidehito Saito, Kumiko Iwabuchi, Noemi Fusaki, Fumito Ito
Adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate durable and complete responses in significant subsets of patients with metastatic melanoma. Major obstacles of this approach are the reduced viability of transferred T cells, caused by telomere shortening, and the limited number of TILs obtained from patients. Less-differentiated T cells with long telomeres would be an ideal T cell subset for adoptive T cell therapy;however, generating large numbers of these less-differentiated T cells is problematic...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910942/improved-bi-allelic-modification-of-a-transcriptionally-silent-locus-in-patient-derived-ipsc-by-cas9-nickase
#5
Reto Eggenschwiler, Mohsen Moslem, Mariane Serra Fráguas, Melanie Galla, Oliver Papp, Maximilian Naujock, Ines Fonfara, Ingrid Gensch, Annabell Wähner, Abbas Beh-Pajooh, Claudio Mussolino, Marcel Tauscher, Doris Steinemann, Florian Wegner, Susanne Petri, Axel Schambach, Emmanuelle Charpentier, Toni Cathomen, Tobias Cantz
Homology directed repair (HDR)-based genome editing via selectable long flanking arm donors can be hampered by local transgene silencing at transcriptionally silent loci. Here, we report efficient bi-allelic modification of a silent locus in patient-derived hiPSC by using Cas9 nickase and a silencing-resistant donor construct that contains an excisable selection/counter-selection cassette. To identify the most active single guide RNA (sgRNA)/nickase combinations, we employed a lentiviral vector-based reporter assay to determine the HDR efficiencies in cella...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910041/efficient-genome-editing-in-induced-pluripotent-stem-cells-with-engineered-nucleases-in-vitro
#6
Vittavat Termglinchan, Timon Seeger, Caressa Chen, Joseph C Wu, Ioannis Karakikes
Precision genome engineering is rapidly advancing the application of the induced pluripotent stem cells (iPSCs) technology for in vitro disease modeling of cardiovascular diseases. Targeted genome editing using engineered nucleases is a powerful tool that allows for reverse genetics, genome engineering, and targeted transgene integration experiments to be performed in a precise and predictable manner. However, nuclease-mediated homologous recombination is an inefficient process. Herein, we describe the development of an optimized method combining site-specific nucleases and the piggyBac transposon system for "seamless" genome editing in pluripotent stem cells with high efficiency and fidelity in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909533/patient-specific-induced-pluripotent-stem-cell-derived-cardiomyocytes-for-drug-development-and-screening-in-catecholaminergic-polymorphic-ventricular-tachycardia
#7
REVIEW
Ben Jehuda Ronen, Barad Lili
Catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia often leading to sudden cardiac death in children and young adults, is characterized by polymorphic/bidirectional ventricular tachycardia induced by adrenergic stimulation associated with emotionally stress or physical exercise. There are two forms of CPVT: 1. CPVT1 is caused by mutations in the RYR2 gene, encoding for ryanodine receptor type 2. CPVT1 is the most common form of CPVT in the population, and is inherited by a dominant mechanism...
August 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27905670/induced-pluripotent-stem-cells-as-a-new-getaway-for-bone-tissue-engineering-a-systematic-review
#8
REVIEW
Farshid Bastami, Pantea Nazeman, Hamidreza Moslemi, Maryam Rezai Rad, Kazem Sharifi, Arash Khojasteh
OBJECTIVES: Mesenchymal stem cells (MSCs) are frequently used for bone regeneration, however, they are limited in quantity. Moreover, their proliferation and differentiation capabilities reduce during cell culture expansion. Potential application of induced pluripotent stem cells (iPSCs) has been reported as a promising alternative source for bone regeneration. This study aimed to systematically review the available literature on osteogenic potential of iPSCs and to discuss methods applied to enhance their osteogenic potential...
December 1, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27904699/generation-of-induced-pluripotent-stem-cells-with-high-efficiency-from-human-embryonic-renal-cortical-cells
#9
Ling Yao, Ruifang Chen, Pu Wang, Qi Zhang, Hailiang Tang, Huaping Sun
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904680/enhancement-of-early-cardiac-differentiation-of-dedifferentiated-fat-cells-by-dimethyloxalylglycine-via-notch-signaling-pathway
#10
Fuhai Li, Zongzhuang Li, Zhi Jiang, Ye Tian, Zhi Wang, Wei Yi, Chenyun Zhang
Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#11
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27898427/cocaine-withdrawal-reduces-gamma-aminobutyric-acid-ergic-transmission-and-gephyrin-expression-at-medial-prefrontal-cortex-in-cocaine-conditioned-place-preference-rats-which-shows-increased-cocaine-seeking
#12
Wenqiong Yang, Hongsheng He, Yan Pan, Falan Duan, Dan Zhao, Bo Hu, Qingzhen Zhou, Wanhong Liu
AIMS: Chronic cocaine abuse decreases the inhibitory synaptic transmission via unknown mechanisms, while pharmacologically augmenting gamma-aminobutyric acid-ergic (GABAergic) transmission attenuates cocaine craving. Here, we propose that prolonged cocaine withdrawal downregulates GABAergic transmission and its important regulator gephyrin in medial prefrontal cortex (mPFC), in cocaine-conditioned place-preference (CPP) rats. METHODS: CPP test, patch clamp, and Western blot analysis are engaged to test this proposal...
November 30, 2016: European Addiction Research
https://www.readbyqxmd.com/read/27898090/lips-a3s-a-human-genomic-site-for-robust-expression-of-inserted-transgenes
#13
Andriana G Kotini, Michel Sadelain, Eirini P Papapetrou
Transgenesis of human pluripotent stem cells (hPSCs) can enable and empower a variety of studies in stem cell research, including lineage tracing and functional genetics studies. While in recent years much progress has been made in the development of tools for gene targeting, little attention has been given to the identification of sites in the human genome where transgenes can be inserted and reliably expressed. In order to find human genomic sites capable of supporting long-term and high-level transgene expression in hPSCs, we performed a lentiviral screen in human induced pluripotent stem cells (iPSCs)...
November 29, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27895584/induced-pluripotent-stem-cells-inhibit-bleomycin-induced-pulmonary-fibrosis-in-mice-through-suppressing-tgf-%C3%AE-1-smad-mediated-epithelial-to-mesenchymal-transition
#14
Yan Zhou, Zhong He, Yuan Gao, Rui Zheng, Xiaoye Zhang, Li Zhao, Mingqi Tan
Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with high mortality and few treatment options. Recently, induced pluripotent stem (iPS) cells have been considered as an ideal resource for stem cell-based therapy. Although, an earlier study demonstrated the therapeutic effect of iPS cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present study investigated the effects of iPS cells on inflammatory responses, transforming growth factor (TGF)-β1 signaling pathway, and epithelial to mesenchymal transition (EMT) during bleomycin (BLM)-induced lung fibrosis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27893734/an-ipsc-derived-vascular-model-of-marfan-syndrome-identifies-key-mediators-of-smooth-muscle-cell-death
#15
Alessandra Granata, Felipe Serrano, William George Bernard, Madeline McNamara, Lucinda Low, Priya Sastry, Sanjay Sinha
Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in FBN1, which encodes the extracellular matrix protein fibrillin-1. To investigate the pathogenesis of aortic aneurysms in MFS, we generated a vascular model derived from human induced pluripotent stem cells (MFS-hiPSCs). Our MFS-hiPSC-derived smooth muscle cells (SMCs) recapitulated the pathology seen in Marfan aortas, including defects in fibrillin-1 accumulation, extracellular matrix degradation, transforming growth factor-β (TGF-β) signaling, contraction and apoptosis; abnormalities were corrected by CRISPR-based editing of the FBN1 mutation...
November 28, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27889084/linking-telomere-regulation-to-stem-cell-pluripotency
#16
REVIEW
Lin Liu
Embryonic stem cells (ESCs), somatic cell nuclear transfer ESCs, and induced pluripotent stem cells (iPSCs) represent the most studied group of PSCs. Unlimited self-renewal without incurring chromosomal instability and pluripotency are essential for the potential use of PSCs in regenerative therapy. Telomere length maintenance is critical for the unlimited self-renewal, pluripotency, and chromosomal stability of PSCs. While telomerase has a primary role in telomere maintenance, alternative lengthening of telomere pathways involving recombination and epigenetic modifications are also required for telomere length regulation, notably in mouse PSCs...
November 23, 2016: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27888626/interleukin-18-deteriorates-fabry-cardiomyopathy-and-contributes-to-the-development-of-left-ventricular-hypertrophy-in-fabry-patients-with-gla-ivs4-919-g-a-mutation
#17
Yueh Chien, Chian-Shiu Chien, Huai-Chih Chiang, Wei-Lin Huang, Shih-Jie Chou, Wei-Chao Chang, Yuh-Lih Chang, Hsin-Bang Leu, Kuan-Hsuan Chen, Kang-Ling Wang, Ying-Hsiu Lai, Yung-Yang Liu, Kai-Hsi Lu, Hsin-Yang Li, Yen-Jen Sung, Yuh-Jyh Jong, Yann-Jang Chen, Chung-Hsuan Chen, Wen-Chung Yu
RATIONALE: A high incidence of GLA IVS4+919 G>A mutation in patients with Fabry disease of the later-onset cardiac phenotype, has been reported in Taiwan. However, suitable biomarkers or potential therapeutic surrogates for Fabry cardiomyopathy (FC) in such patients under enzyme replacement treatment (ERT) remain unknown. OBJECTIVE: Using FC patients carrying IVS4+919 G>A mutation, we constructed an induced pluripotent stem cell (iPSC)-based disease model to investigate the pathogenetic biomarkers and potential therapeutic targets in ERT-treated FC...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888517/differentiation-of-induced-pluripotent-stem-cell-derived-neutrophil-granulocytes-from-common-marmoset-monkey-callithrix-jacchus
#18
Christopher Schrimpf, Christoph Wrede, Silke Glage, Jan Hegermann, Samantha Backhaus, Rainer Blasczyk, Hans-Gert Heuft, Thomas Müller
BACKGROUND: Inherited and acquired marrow failure syndromes most commonly lead to defect in myeloid and/or neutrophil differentiation and/or function. Besides this, neutropenia induced by cancer-adjusted chemotherapy is a frequent clinical problem. In both cases, cell replacement therapy is a well-established, but due to necessity of donors limited and perilous procedure. Therefore, autologous cell replacement from patients' own marrow-derived cells lowers risk and bares new possibilities for therapy...
November 25, 2016: Transfusion
https://www.readbyqxmd.com/read/27886004/influence-of-surface-roughness-on-neural-differentiation-of-human-induced-pluripotent-stem-cells
#19
Zhengdong Li, Weiwei Wang, Karl Kratz, Judit Küchler, Xun Xu, Jie Zou, Deng Zijun, Xianlei Sun, Manfred Gossen, Nan Ma, Andreas Lendlein
Induced pluripotent stem cells (iPSCs) own the capacity to develop into all cell types of the adult body, presenting high potential in regenerative medicine. Regulating and controlling the differentiation of iPSCs using the surface topographic cues of biomaterials is a promising and safe approach to enhance their therapeutic efficacy. In this study, we tested the effects of surface roughness on differentiation of human iPSCs into neural progenitor cells and dopaminergic neuron cells using polystyrene with different roughness (R0: flat surface; R1: rough surface, Rq ∼ 6 μm; R2: rough surface, Rq ∼ 38 μm)...
November 23, 2016: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/27885898/ipsc-in-the-past-decade-the-japanese-dominance
#20
Dusko Ilic
No abstract text is available yet for this article.
December 2016: Regenerative Medicine
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