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Induced pluripotent stem

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https://www.readbyqxmd.com/read/28731526/drug-discovery-and-development-for-rare-genetic-disorders
#1
REVIEW
Wei Sun, Wei Zheng, Anton Simeonov
Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed...
July 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28731447/chromatin-bound-oxidized-%C3%AE-synuclein-causes-strand-breaks-in-neuronal-genomes-in-in-vitro-models-of-parkinson-s-disease
#2
Velmarini Vasquez, Joy Mitra, Pavana M Hegde, Arvind Pandey, Shiladitya Sengupta, Sankar Mitra, K S Rao, Muralidhar L Hegde
Alpha-synuclein (α-Syn) overexpression and misfolding/aggregation in degenerating dopaminergic neurons have long been implicated in Parkinson's disease (PD). The neurotoxicity of α-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Although α-Syn is predominantly localized in presynaptic nerve terminals, a small fraction exists in neuronal nuclei. However, the functional and/or pathological role of nuclear α-Syn is unclear. Following up on our earlier report that α-Syn directly binds DNA in vitro, here we confirm the nuclear localization and chromatin association of α-Syn in neurons using proximity ligation and chromatin immunoprecipitation analysis...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28730390/expression-of-type-i-cannabinoid-receptors-at-different-stages-of-neuronal-differentiation-of-human-fibroblasts
#3
M Yu Bobrov, V V Bezuglov, L G Khaspekov, S N Illarioshkin, E V Novosadova, I A Grivennikov
Differential expression of type 1 cannabinoid receptors (CR1) was evaluated at different stages of human skin fibroblast transformation into terminally differentiated neurons. Immunocytochemical staining detected no CR1 on fibroblasts, but their transformation into induced pluripotent stem cells was accompanied by marked stimulation of CR1 expression. In neuronal precursors, the receptors were located mainly on cell bodies and at the base of their processes. This distribution was retained at the terminal stage of differentiation of induced pluripotent stem cells into neurons...
July 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28729840/cardiac-subtype-specific-modeling-of-kv1-5-ion-channel-deficiency-using-human-pluripotent-stem-cells
#4
Maike Marczenke, Ilaria Piccini, Isabella Mengarelli, Jakob Fell, Albrecht Röpke, Guiscard Seebohm, Arie O Verkerk, Boris Greber
The ultrarapid delayed rectifier K(+) current (IKur), mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF). Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs) to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28729666/expansion-of-human-midbrain-floor-plate-progenitors-from-induced-pluripotent-stem-cells-increases-dopaminergic-neuron-differentiation-potential
#5
Stefania Fedele, Ginetta Collo, Katharina Behr, Josef Bischofberger, Stephan Müller, Tilo Kunath, Klaus Christensen, Anna Lisa Gündner, Martin Graf, Ravi Jagasia, Verdon Taylor
Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729365/induced-pluripotent-stem-cell-derived-endothelial-cells-in-insulin-resistance-and-metabolic-syndrome
#6
REVIEW
Ivan Carcamo-Orive, Ngan F Huang, Thomas Quertermous, Joshua W Knowles
Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28728561/understanding-the-genetics-behind-complex-human-disease-with-large-scale-ipsc-collections
#7
Amanda E Yamasaki, Athanasia D Panopoulos, Juan Carlos Izpisua Belmonte
Three recent studies analyzing large-scale collections of human induced pluripotent stem cell lines provide valuable insight into how genetic regulatory variation affects cellular and molecular traits.
July 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/28727686/fbxw7-regulates-disc1-stability-via-the-ubiquitin-proteosome-system
#8
K Yalla, C Elliott, J P Day, J Findlay, S Barratt, Z A Hughes, L Wilson, E Whiteley, M Popiolek, Y Li, J Dunlop, R Killick, D R Adams, N J Brandon, M D Houslay, B Hao, G S Baillie
Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28726548/wnt-yap-interactions-during-neural-tissue-patterning-of-human-induced-pluripotent-stem-cells
#9
Julie Bejoy, Liqing Song, Yi Zhou, Yan Li
Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests...
July 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28726546/nanotopographic-influence-on-the-in-vitro-behavior-of-induced-pluripotent-stem-cells
#10
Ji-Yun Ko, Hyun-Jik Oh, Jimin Lee, Gun-Il Im
While the influence of nanotopography on stem cell behavior have been extensively investigated on adult stem cells, far fewer studies have investigated the interaction of induced pluripotent stem cells (iPSC) with various nanotopographical patterns. The purpose of this study was to identify nanopatterns that can influence the stemness and proliferation as well as the adhesive properties in iPSCs, and thereby explore the feasibility of applying these nano-features for regenerative medicine. Three kinds of nanopatterns were fabricated from polydimethylsiloxane (PDMS) membranes, irregular patterned membrane (IPM), groove patterned membrane (GPM), and post patterned membrane (PPM), in addition to flat patterned membrane (FPM) which did not have any nanotopographic features and was used as the control pattern...
July 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28726153/immunological-issues-after-stem-cell-based-%C3%AE-cell-replacement
#11
REVIEW
Valeria Sordi, Silvia Pellegrini, Lorenzo Piemonti
PURPOSE OF REVIEW: Islet and pancreas transplantation prove that β cell replacement can cure the glycemic derangements in type 1 diabetes (T1D). Induced pluripotent stem cells (iPSCs) can differentiate into functional insulin-producing cells, able to restore normoglycemia in diabetic animal models. iPSCs in particular can be derived from the somatic cells of a person with T1D. This review aims to clarify if it is possible to transplant autologous iPSC-derived β cells without immunosuppression or which are the alternative approaches...
September 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28725655/cell-replacement-therapy-is-the-remedial-solution-for-treating-parkinson-s-disease
#12
REVIEW
Venkatesan Dhivya, Vellingiri Balachandar
The selective degeneration of dopaminergic (DA) neurons in Parkinson's disease (PD) has made an idol target for cell replacement therapies and other emerging surgical treatments. Certainly, by transplantation method, the therapeutic regimens such as human fetal ventral midbrain (hfVM) cells, human embryonic stem cells (hESCs), human neural stem/precursor/ progenitor cells (hNSCs/hNPCs), human mesenchymal stem cells (hMSCs), human induced neural stem cells (hiNSCs), and human induced pluripotent stem cells (hiPSCs) have been used into DA deficient striatum...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28725651/human-acute-leukemia-induced-pluripotent-stem-cells-a-unique-model-for-investigating-disease-development-and-pathogenesis
#13
EDITORIAL
Clara Bueno, Pablo Menendez
No abstract text is available yet for this article.
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28725649/inducible-pluripotent-stem-cells-and-pulmonary-arterial-hypertension-the-future-is-now
#14
EDITORIAL
Monica Romero Lopez, Vinicio de Jesus Perez
No abstract text is available yet for this article.
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28724793/a-bag3-chaperone-complex-maintains-cardiomyocyte-function-during-proteotoxic-stress
#15
Luke M Judge, Juan A Perez-Bermejo, Annie Truong, Alexandre Js Ribeiro, Jennie C Yoo, Christina L Jensen, Mohammad A Mandegar, Nathaniel Huebsch, Robyn M Kaake, Po-Lin So, Deepak Srivastava, Beth L Pruitt, Nevan J Krogan, Bruce R Conklin
Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28723550/induced-pluripotent-stem-cell-derived-primitive-macrophages-provide-a-platform-for-modeling-tissue-resident-macrophage-differentiation-and-function
#16
Kazuyuki Takata, Tatsuya Kozaki, Christopher Zhe Wei Lee, Morgane Sonia Thion, Masayuki Otsuka, Shawn Lim, Kagistia Hana Utami, Kerem Fidan, Dong Shin Park, Benoit Malleret, Svetoslav Chakarov, Peter See, Donovan Low, Gillian Low, Marta Garcia-Miralles, Ruizhu Zeng, Jinqiu Zhang, Chi Ching Goh, Ahmet Gul, Sandra Hubert, Bernett Lee, Jinmiao Chen, Ivy Low, Nurhidaya Binte Shadan, Josephine Lum, Tay Seok Wei, Esther Mok, Shohei Kawanishi, Yoshihisa Kitamura, Anis Larbi, Michael Poidinger, Laurent Renia, Lai Guan Ng, Yochai Wolf, Steffen Jung, Tamer Önder, Evan Newell, Tara Huber, Eishi Ashihara, Sonia Garel, Mahmoud A Pouladi, Florent Ginhoux
Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28722778/breast-cancer-stem-cells-are-involved-in-trastuzumab-resistance-through-the-her2-modulation-in-3d-culture
#17
Cristina Elisa Rodríguez, Damian Emilio Berardi, Marianela Abrigo, Laura Beatriz Torado, Elisa Dora Bal de Kier Joffé, Gabriel León Fiszman
Breast cancer human cells culture as spheroids develop autophagy and apoptosis, which promotes Trastuzumab resistance in HER2 overexpressing cells. Our aim was to study the association of the hostile environment developed in 3D with the breast cancer stem cells population and the HER2 modulation. Human mammary adenocarcinoma cell lines were cultured as spheroids using the hanging drop method. We generated hypoxia conditions by using a hypoxic chamber and CoCl2 treatment. Breast cancer stem cells were measured with mammosphere assays, the analysis of CD44 + CD24(low) population by flow cytometry and the pluripotent gene expression by RT-qPCR...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28722510/bnip3l-dependent-mitophagy-accounts-for-mitochondrial-clearance-during-three-factors-induced-somatic-cell-reprogramming
#18
Ge Xiang, Liang Yang, Qi Long, Keshi Chen, Haite Tang, Yi Wu, Zihuang Liu, Yanshuang Zhou, Juntao Qi, Lingjun Zheng, Wenbo Liu, Zhongfu Ying, Weimin Fan, Hongyan Shi, Hongmei Li, Xiaobing Lin, Mi Gao, Jinglei Liu, Feixiang Bao, Linpeng Li, Lifan Duan, Min Li, Xingguo Liu
Induced pluripotent stem cells (iPSCs) have less and immature mitochondria than somatic cells and mainly rely on glycolysis for energy source. During somatic cell reprogramming, somatic mitochondria and other organelles get remodeled. However, events of organelle remodeling and interaction during somatic cell reprogramming have not been extensively explored. We show that both SKP/SKO (Sox2, Klf4, Pou5f1/Oct4) and SKPM/SKOM (SKP/SKO plus Myc/c-Myc) reprogramming lead to decreased mitochondrial mass but with different kinetics and by divergent pathways...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28721524/human-ipsc-derived-cardiomyocytes-for-investigation-of-disease-mechanisms-and-therapeutic-strategies-in-inherited-arrhythmia-syndromes-strengths-and-limitations
#19
Simona Casini, Arie O Verkerk, Carol Ann Remme
During the last two decades, significant progress has been made in the identification of genetic defects underlying inherited arrhythmia syndromes, which has provided some clinical benefit through elucidation of gene-specific arrhythmia triggers and treatment. However, for most arrhythmia syndromes, clinical management is hindered by insufficient knowledge of the functional consequences of the mutation in question, the pro-arrhythmic mechanisms involved, and hence the most optimal treatment strategy. Moreover, disease expressivity and sensitivity to therapeutic interventions often varies between mutations and/or patients, underlining the need for more individualized strategies...
July 18, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28720304/characterization-of-the-single-cell-derived-bovine-induced-pluripotent-stem-cells
#20
Lixia Zhao, Zixin Wang, Jindun Zhang, Jian Yang, Xuefei Gao, Baojiang Wu, Gaoping Zhao, Siqin Bao, Shuxiang Hu, Pentao Liu, Xihe Li
Single-cell derived bovine induced pluripotent stem cells (iPSCs) were generated by the introduction of piggyBac transposons with CAG promoting transcription factors (Oct3/4, Sox2, Klf4 and cMyc). In the study, the bovine iPSCs colony from single cell could passage more than 50 passages after enzymatic dissociation into single cells. These bovine iPSCs cells kept the normal karyotype and displayed dome shaped clones similar to mouse embryonic stem cells. They showed pluripotency in many ways, including their expression of pluripotency markers, such as OCT3/4, NANOG, SOX2, SSEA1, SSEA4, and AP in immunofluorescence assay, Oct4, Nanog, Sox2, Klf4 and cMyc in RT-PCR...
May 22, 2017: Tissue & Cell
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