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Direct Reprogramming

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https://www.readbyqxmd.com/read/27917895/small-molecules-increase-direct-neural-conversion-of-human-fibroblasts
#1
Ulrich Pfisterer, Fredrik Ek, Stefan Lang, Shamit Soneji, Roger Olsson, Malin Parmar
The generation of human induced neurons (hiNs) via exogenous delivery of neural transcription factors represents a novel technique to obtain disease and patient specific neurons. These cells have the potential to be used for disease modeling, diagnostics and drug screening, and also to be further developed for brain repair. In the present study, we utilized hiNs to develop an unbiased screening assay for small molecules that increase the conversion efficiency. Using this assay, we screened 307 compounds from five annotated libraries and identified six compounds that were very potent in potentiating the reprogramming process...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917881/distinct-and-shared-determinants-of-cardiomyocyte-contractility-in-multi-lineage-competent-ethnically-diverse-human-ipscs
#2
Martin L Tomov, Zachary T Olmsted, Haluk Dogan, Eda Gongorurler, Maria Tsompana, Hasan H Otu, Michael Buck, Eun-Ah Chang, Jose Cibelli, Janet L Paluh
The realization of personalized medicine through human induced pluripotent stem cell (iPSC) technology can be advanced by transcriptomics, epigenomics, and bioinformatics that inform on genetic pathways directing tissue development and function. When possible, population diversity should be included in new studies as resources become available. Previously we derived replicate iPSC lines of African American, Hispanic-Latino and Asian self-designated ethnically diverse (ED) origins with normal karyotype, verified teratoma formation, pluripotency biomarkers, and tri-lineage in vitro commitment...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27915387/the-translational-potential-of-human%C3%A2-induced-pluripotent-stem-cells-for-clinical-neurology-the-translational-potential-of-hipscs-in-neurology
#3
REVIEW
Helen Devine, Rickie Patani
The induced pluripotent state represents a decade-old Nobel prize-winning discovery. Human-induced pluripotent stem cells (hiPSCs) are generated by the nuclear reprogramming of any somatic cell using a variety of established but evolving methods. This approach offers medical science unparalleled experimental opportunity to model an individual patient's disease "in a dish." HiPSCs permit developmentally rationalized directed differentiation into any cell type, which express donor cell mutation(s) at pathophysiological levels and thus hold considerable potential for disease modeling, drug discovery, and potentially cell-based therapies...
December 3, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27915033/survivin-controls-biogenesis-of-microrna-in-smokers-a-link-to-pathogenesis-of-rheumatoid-arthritis
#4
Karin M E Andersson, Minna Turkkila, Malin C Erlandsson, Apostolos Bossios, Sofia Töyrä Silfverswärd, Dan Hu, Linda Ekerljung, Carina Malmhäll, Howard L Weiner, Bo Lundbäck, Maria I Bokarewa
MicroRNAs (miRs) represent a part of epigenetic control of autoimmunity gaining increasing attention in rheumatoid arthritis (RA). Since cigarette smoking plays important role in RA pathogenesis and reprograms transcriptional profile of miRNAs, we ask if the onco-protein survivin, a novel biomarker of RA, may provide a link between smoking and miRNA. Studying survivin expression in leukocytes of 144 female RA patients we observed that smoking patients had higher survivin transcription and a remarkable spreading of survivin isoforms...
November 30, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27911861/pyruvate-kinase-m2-pkm2-expression-correlates-with-prognosis-in-solid-cancers-a-meta-analysis
#5
Haiyan Zhu, Hui Luo, Xuejie Zhu, Xiaoli Hu, Lihong Zheng, Xueqiong Zhu
Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910042/direct-cardiac-reprogramming-as-a-novel-therapeutic-strategy-for-treatment-of-myocardial-infarction
#6
Hong Ma, Li Wang, Jiandong Liu, Li Qian
Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27906098/direct-reprogramming-of-urine-derived-cells-with-inducible-myod-for-modeling-human-muscle-disease
#7
Ellis Y Kim, Patrick Page, Lisa M Dellefave-Castillo, Elizabeth M McNally, Eugene J Wyatt
BACKGROUND: Cellular models of muscle disease are taking on increasing importance with the large number of genes and mutations implicated in causing myopathies and the concomitant need to test personalized therapies. Developing cell models relies on having an easily obtained source of cells, and if the cells are not derived from muscle itself, a robust reprogramming process is needed. Fibroblasts are a human cell source that works well for the generation of induced pluripotent stem cells, which can then be differentiated into cardiomyocyte lineages, and with less efficiency, skeletal muscle-like lineages...
September 15, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27902735/role-of-hepatic-specific-transcription-factors-and-polycomb-repressive-complex-2-during-induction-of-fibroblasts-to-hepatic-fate
#8
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Abdulshakour Mohammadnia, Moein Yaqubi
Direct reprogramming using defined sets of transcription factors (TFs) is a recent strategy for generating induced hepatocytes (iHeps) from fibroblasts for use in regenerative medicine and drug development. Comprehensive studies detailing the regulatory role of TFs during this reprogramming process could help increase its efficiency. This study aimed to find the TFs with the greatest influences on the generation of iHeps from fibroblasts, and to further understand their roles in the regulation of the gene expression program...
2016: PloS One
https://www.readbyqxmd.com/read/27901044/fatty-acid-metabolic-reprogramming-via-mtor-mediated-inductions-of-ppar%C3%AE-directs-early-activation-of-t-cells
#9
Mulki Angela, Yusuke Endo, Hikari K Asou, Takeshi Yamamoto, Damon J Tumes, Hirotake Tokuyama, Koutaro Yokote, Toshinori Nakayama
To fulfil the bioenergetic requirements for increased cell size and clonal expansion, activated T cells reprogramme their metabolic signatures from energetically quiescent to activated. However, the molecular mechanisms and essential components controlling metabolic reprogramming in T cells are not well understood. Here, we show that the mTORC1-PPARγ pathway is crucial for the fatty acid uptake programme in activated CD4(+) T cells. This pathway is required for full activation and rapid proliferation of naive and memory CD4(+) T cells...
November 30, 2016: Nature Communications
https://www.readbyqxmd.com/read/27900567/clinical-potential-of-human-induced-pluripotent-stem-cells-perspectives-of-induced-pluripotent-stem-cells
#10
REVIEW
Dharmendra Kumar, Taruna Anand, Wilfried A Kues
The recent establishment of induced pluripotent stem (iPS) cells promises the development of autologous cell therapies for degenerative diseases, without the ethical concerns associated with human embryonic stem (ES) cells. Initially, iPS cells were generated by retroviral transduction of somatic cells with core reprogramming genes. To avoid potential genotoxic effects associated with retroviral transfection, more recently, alternative non-viral gene transfer approaches were developed. Before a potential clinical application of iPS cell-derived therapies can be planned, it must be ensured that the reprogramming to pluripotency is not associated with genome mutagenesis or epigenetic aberrations...
November 29, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27893319/insight-into-the-machinery-that-oils-chromatin-dynamics
#11
Roni H G Wright, Narcis Fernandez-Fuentes, Baldomero Oliva, Miguel Beato
The packaging of genetic information in form of chromatin within the nucleus provides cells with the ability to store and protect massive amounts of information within a compact space. Storing information within chromatin allows selective access to specific DNA sequences by regulating the various levels of chromatin structure from nucleosomes, to chromatin fibers, loops and topological associating domains (TADs) using mechanisms that are being progressively unravelled. However, a relatively unexplored aspect is the energetic cost of changing the chromatin configuration to gain access to DNA information...
November 28, 2016: Nucleus
https://www.readbyqxmd.com/read/27892643/the-rice-osnac6-transcription-factor-orchestrates-multiple-molecular-mechanisms-involving-root-structural-adaptions-and-nicotianamine-biosynthesis-for-drought-tolerance
#12
Dong-Keun Lee, Pil Joong Chung, Jin Seo Jeong, Geupil Jang, Seung Woon Bang, Harin Jung, Youn Shic Kim, Sun-Hwa Ha, Yang Do Choi, Ju-Kon Kim
Drought has a serious impact on agriculture worldwide. A plant's ability to adapt to rhizosphere drought stress requires reprograming of root growth and development. Although physiological studies have documented the root adaption for tolerance to the drought stress, underlying molecular mechanisms is still incomplete, which is essential for crop engineering. Here, we identified OsNAC6-mediated root structural adaptations, including increased root number and root diameter, which enhanced drought tolerance. Multiyear drought field tests demonstrated that the grain yield of OsNAC6 root-specific overexpressing transgenic rice lines was less affected by drought stress than were non-transgenic controls...
November 28, 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/27890924/cellular-plasticity-in-kidney-injury-and-repair
#13
REVIEW
Monica Chang-Panesso, Benjamin D Humphreys
Terminally differentiated cells can be reprogrammed to pluripotency or directly to another differentiated cell type in vitro, a capacity termed cellular plasticity. Plasticity is not limited to in vitro manipulations but rather represents an important aspect of the regenerative response to injury in organs. Differentiated adult cells retain the capacity to dedifferentiate, adopting a progenitor-like phenotype after injury or, alternatively, to transdifferentiate, directly converting to a different mature cell type...
November 28, 2016: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27888287/wnt-signaling-and-cellular-metabolism-in-osteoblasts
#14
REVIEW
Courtney M Karner, Fanxin Long
The adult human skeleton is a multifunctional organ undergoing continuous remodeling. Homeostasis of bone mass in a healthy adult requires an exquisite balance between bone resorption by osteoclasts and bone formation by osteoblasts; disturbance of such balance is the root cause for various bone disorders including osteoporosis. To develop effective and safe therapeutics to modulate bone formation, it is essential to elucidate the molecular mechanisms governing osteoblast differentiation and activity. Due to their specialized function in collagen synthesis and secretion, osteoblasts are expected to consume large amounts of nutrients...
November 26, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27886180/microrna-regulation-of-endothelial-trex1-reprograms-the-tumour-microenvironment
#15
RaeAnna Wilson, Cristina Espinosa-Diez, Nathan Kanner, Namita Chatterjee, Rebecca Ruhl, Christina Hipfinger, Sunil J Advani, Jie Li, Omar F Khan, Aleksandra Franovic, Sara M Weis, Sushil Kumar, Lisa M Coussens, Daniel G Anderson, Clark C Chen, David A Cheresh, Sudarshan Anand
Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth...
November 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27879215/a-human-ve-cadherin-tdtomato-and-cd43-green-fluorescent-protein-dual-reporter-cell-line-for-study-endothelial-to-hematopoietic-transition
#16
Ho Sun Jung, Gene Uenishi, Akhilesh Kumar, Mi Ae Park, Matt Raymond, Dustin Fink, Ethan McLeod, Igor Slukvin
Human embryonic stem cell line WA01 was genetically modified using zinc-finger nucleases and the PiggyBac/transponson system to introduce a fluorescence reporter for VE-cadherin (VEC; tdTomato) and CD43 (eGFP). Phenotypic and functional assays for pluripotency revealed the modified hES cell reporter lines remained normal. When the cells were differentiated into hematoendothelial lineages, either by directed differentiation or direct reprogramming, flow cytometric and fluorescence microscopy showed that VEC+ endothelial cells express tdTomato and CD43+ hematopoietic progenitors express eGFP...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27876670/a-model-of-dynamic-stability-of-h3k9me3-heterochromatin-to-explain-the-resistance-to-reprogramming-of-differentiated-cells
#17
Charly Jehanno, Gilles Flouriot, Pascale Le Goff, Denis Michel
Despite their dynamic nature, certain chromatin marks must be maintained over the long term. This is particulary true for histone 3 lysine 9 (H3K9) trimethylation, that is involved in the maintenance of healthy differentiated cellular states by preventing inappropriate gene expression, and has been recently identified as the most efficient barrier to cellular reprogramming in nuclear transfer experiments. We propose that the capacity of the enzymes SUV39H1/2 to rebind to a minor fraction of their products, either directly or via HP1α/β, contributes to the solidity of this mark through (i) a positive feedback involved in its establishment by the mutual enforcement of H3K9me3 and SUV39H1/2 and then (ii) a negative feedback sufficient to strongly stabilize H3K9me3 heterochromatin in post-mitotic cells by generating local enzyme concentrations capable of counteracting transient bursts of demethylation...
November 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27860374/chemoprevention-of-obesity-by-dietary-natural-compounds-targeting-mitochondrial-regulation
#18
REVIEW
Ching-Shu Lai, Jia-Ching Wu, Chi-Tang Ho, Min-Hsiung Pan
Mitochondria are center stage in the control of energy homeostasis in many organs and tissue including adipose tissue. Recently, abundant evidences from experimental studies have clearly supported the strong correlation between mitochondrial dysfunction in adipocytes and obesity. Various physiological conditions, such as excessive nutrition, genetic factors, hypoxia and toxins disrupt mitochondrial function by impairing mitochondrial biogenesis, dynamics and oxidative capacity. Mitochondrial dysfunction in adipocytes could have impact on differentiation, adipogenesis, insulin sensitivity and with the significant alteration in their metabolic function, which ultimately results in obesity and type 2 diabetes...
November 16, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27857227/how-a-high-gradient-magnetic-field-could-affect-cell-life
#19
Vitalii Zablotskii, Tatyana Polyakova, Oleg Lunov, Alexandr Dejneka
The biological effects of high-gradient magnetic fields (HGMFs) have steadily gained the increased attention of researchers from different disciplines, such as cell biology, cell therapy, targeted stem cell delivery and nanomedicine. We present a theoretical framework towards a fundamental understanding of the effects of HGMFs on intracellular processes, highlighting new directions for the study of living cell machinery: changing the probability of ion-channel on/off switching events by membrane magneto-mechanical stress, suppression of cell growth by magnetic pressure, magnetically induced cell division and cell reprograming, and forced migration of membrane receptor proteins...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27857203/rapid-and-efficient-crispr-cas9-gene-inactivation-in-human-neurons-during-human-pluripotent-stem-cell-differentiation-and-direct-reprogramming
#20
Alicia Rubio, Mirko Luoni, Serena G Giannelli, Isabella Radice, Angelo Iannielli, Cinzia Cancellieri, Claudia Di Berardino, Giulia Regalia, Giovanna Lazzari, Andrea Menegon, Stefano Taverna, Vania Broccoli
The CRISPR/Cas9 system is a rapid and customizable tool for gene editing in mammalian cells. In particular, this approach has widely opened new opportunities for genetic studies in neurological disease. Human neurons can be differentiated in vitro from hPSC (human Pluripotent Stem Cells), hNPCs (human Neural Precursor Cells) or even directly reprogrammed from fibroblasts. Here, we described a new platform which enables, rapid and efficient CRISPR/Cas9-mediated genome targeting simultaneously with three different paradigms for in vitro generation of neurons...
November 18, 2016: Scientific Reports
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