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Direct Reprogramming

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https://www.readbyqxmd.com/read/28529134/direct-reprogramming-epigenetics-and-cardiac-regeneration
#1
REVIEW
Shota Kurotsu, Takeshi Suzuki, Masaki Ieda
The discovery of induced pluripotent stem cells (iPSCs) has revolutionized regenerative medicine. Autologous iPSCs can be generated by introducing 4 stem cell-specific factors (Oct4, Sox2, Klf4, c-Myc) into fibroblasts. iPSCs can propagate indefinitely and differentiate into clinically important cell types including cardiomyocytes, in vitro. The iPSC-derived cardiomyocytes represent a promising source of cells for cell-based therapeutic approaches for cardiac regeneration. However, there are several challenges in the clinical application of iPSCs: tumorigenicity of immature cells, poor survival of the transplanted myocardial cells, and cost and efficacy of this therapeutic approach...
May 18, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28526819/systematic-comparison-of-2a-peptides-for-cloning-multi-genes-in-a-polycistronic-vector
#2
Ziqing Liu, Olivia Chen, J Blake Joseph Wall, Michael Zheng, Yang Zhou, Li Wang, Haley Ruth Vaseghi, Li Qian, Jiandong Liu
Cloning of multiple genes in a single vector has greatly facilitated both basic and translational studies that require co-expression of multiple factors or multi-units of complex protein. Many strategies have been adopted, among which 2A "self-cleaving" peptides have garnered increased interest for their polycistronic nature, small size and high "cleavage" efficiency. However, broad application of 2 A peptides is limited by the lack of systematic comparison of different 2As alone or in combination. Here we characterized the effect of varying gene position and 2As on the expression of proteins encoded in bi-, tri-, or quad-cistronic constructs...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28523248/the-keap1-nrf2-system-in-cancer
#3
REVIEW
Keiko Taguchi, Masayuki Yamamoto
Cancer cells first adapt to the microenvironment and then propagate. Mutations in tumor suppressor genes or oncogenes are frequently found in cancer cells. Comprehensive genomic analyses have identified somatic mutations and other alterations in the KEAP1 or NRF2 genes and in well-known tumor suppressor genes or oncogenes, such as TP53, CDKN2A, PTEN, and PIK3CA, in various types of cancer. Aberrant NRF2 activation in cancer cells occurs through somatic mutations in the KEAP1 or NRF2 gene as well as through other mechanisms that disrupt the binding of KEAP1 to NRF2...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28515784/improving-saccharomyces-cerevisiae-ethanol-production-and-tolerance-via-rna-polymerase-ii-subunit-rpb7
#4
Zilong Qiu, Rongrong Jiang
BACKGROUND: Classical strain engineering methods often have limitations in altering multigenetic cellular phenotypes. Here we try to improve Saccharomyces cerevisiae ethanol tolerance and productivity by reprogramming its transcription profile through rewiring its key transcription component RNA polymerase II (RNAP II), which plays a central role in synthesizing mRNAs. This is the first report on using directed evolution method to engineer RNAP II to alter S. cerevisiae strain phenotypes...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28515464/systems-immunology-of-diabetes-tuberculosis-comorbidity-reveals-signatures-of-disease-complications
#5
Cesar A Prada-Medina, Kiyoshi F Fukutani, Nathella Pavan Kumar, Leonardo Gil-Santana, Subash Babu, Flávio Lichtenstein, Kim West, Shanmugam Sivakumar, Pradeep A Menon, Vijay Viswanathan, Bruno B Andrade, Helder I Nakaya, Hardy Kornfeld
Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515438/mitochondrial-retrograde-signaling-connects-respiratory-capacity-to-thermogenic-gene-expression
#6
Minwoo Nam, Thomas E Akie, Masato Sanosaka, Siobhan M Craige, Shashi Kant, John F Keaney, Marcus P Cooper
Mitochondrial respiration plays a crucial role in determining the metabolic state of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well as through additional mechanisms. Here, we show that respiration-dependent retrograde signaling from mitochondria to nucleus contributes to genetic and metabolic reprogramming of BAT. In mouse BAT, ablation of LRPPRC (LRP130), a potent regulator of mitochondrial transcription and respiratory capacity, triggers down-regulation of thermogenic genes, promoting a storage phenotype in BAT...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514443/cancer-progression-by-reprogrammed-bcaa-metabolism-in-myeloid-leukaemia
#7
Ayuna Hattori, Makoto Tsunoda, Takaaki Konuma, Masayuki Kobayashi, Tamas Nagy, John Glushka, Fariba Tayyari, Daniel McSkimming, Natarajan Kannan, Arinobu Tojo, Arthur S Edison, Takahiro Ito
Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28509990/transient-activation-of-reprogramming-transcription-factors-using-protein-transduction-facilitates-conversion-of-human-fibroblasts-toward-cardiomyocyte-like-cells
#8
Zaniar Ghazizadeh, Hassan Rassouli, Hananeh Fonoudi, Mehdi Alikhani, Mahmood Talkhabi, Amir Darbandi-Azar, Shuibing Chen, Hossein Baharvand, Nasser Aghdami, Ghasem Hosseini Salekdeh
Derivation of cardiomyocytes directly from patients' own fibroblasts could offer a new therapeutic approach for those with ischemic heart disease. An essential step toward clinical application is to establish safe conversion of human fibroblasts into a cardiac fate. Here we aimed to efficiently and safely generate cardiomyocytes from human fibroblasts by direct delivery of reprogramming recombinant cell permeant form of reprogramming proteins followed by cardio-inductive signals. Human fetal and adult fibroblasts were transiently exposed to transactivator of transcription-fused recombinant OCT4, SOX2, KLF4 and c-MYC for 2 weeks and then were directly differentiated toward protein-induced cardiomyocyte-like cells (p-iCLCs) in a cardiac fate niche, carried out by treatment with a set of cardiogenic small molecules (sequential treatment of Chir, and IWP-2, SB431542 and purmorphamine)...
May 16, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28509532/nanodiamonds-mediate-oral-delivery-of-proteins-for-stem-cell-activation-and-intestinal-remodeling-in-drosophila
#9
Xingjie Hu, Xiaojiao Li, Min Yin, Ping Li, Ping Huang, Lihua Wang, Yiguo Jiang, Hui Wang, Nan Chen, Chunhai Fan, Haiyun Song
Introduction of exogenous biomacromolecules into living systems is of great interest in genome editing, cancer immunotherapy, and stem cell reprogramming. Whereas current strategies generally depend on nucleic acids transfection, direct delivery of functional proteins that provides enhanced specificity, increased safety, and fast and temporal regulation is highly desirable. Nevertheless, intracellular delivery of intact and bioactive proteins, especially in vivo, remains poorly explored. In this study, we developed a nanodiamonds (NDs)-based protein delivery system in cultured cells and in Drosophila that showed high adsorption, high efficiency, and effective cytosolic release of fully functional proteins...
May 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28502796/in-vivo-reprogramming-for-heart-regeneration-a-glance-at-efficiency-environmental-impacts-challenges-and-future-directions
#10
REVIEW
Behnam Ebrahimi
Replacing dying or diseased cells of a tissue with new ones that are converted from patient's own cells is an attractive strategy in regenerative medicine. In vivo reprogramming is a novel strategy that can circumvent the hurdles of autologous/allogeneic cell injection therapies. Interestingly, studies have demonstrated that direct injection of cardiac transcription factors or specific miRNAs into the infarct border zone of murine hearts following myocardial infarction converts resident cardiac fibroblasts into functional cardiomyocytes...
May 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28501509/designer-outer-membrane-vesicles-as-immunomodulatory-systems-reprogramming-bacteria-for-vaccine-delivery
#11
Yehou M D Gnopo, Hannah C Watkins, Taylor C Stevenson, Matthew P DeLisa, David Putnam
Vaccines often require adjuvants to be effective. Traditional adjuvants, like alum, activate the immune response but in an uncontrolled way. Newer adjuvants help to direct the immune response in a more coordinated fashion. Here, we review the opportunity to use the outer membrane vesicles (OMVs) of bacteria as a way to modulate the immune response toward making more effective vaccines. This review outlines the different types of OMVs that have been investigated for vaccine delivery and how they are produced...
May 10, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28487429/rationally-designed-tlr4-ligands-for-vaccine-adjuvant-discovery
#12
Kelsey A Gregg, Erin Harberts, Francesca M Gardner, Mark R Pelletier, Corinne Cayatte, Li Yu, Michael P McCarthy, Jason D Marshall, Robert K Ernst
Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A) are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC) as a method to generate rationally designed, functionally diverse lipid A...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28484188/c-to-u-editing-and-site-directed-rna-editing-for-the-correction-of-genetic-mutations
#13
Luyen Thi Vu, Toshifumi Tsukahara
Cytidine to uridine (C-to-U) editing is one type of substitutional RNA editing. It occurs in both mammals and plants. The molecular mechanism of C-to-U editing involves the hydrolytic deamination of a cytosine to a uracil base. C-to-U editing is mediated by RNA-specific cytidine deaminases and several complementation factors, which have not been completely identified. Here, we review recent findings related to the regulation and enzymatic basis of C-to-U RNA editing. More importantly, when C-to-U editing occurs in coding regions, it has the power to reprogram genetic information on the RNA level, therefore it has great potential for applications in transcript repair (diseases related to thymidine to cytidine (T>C) or adenosine to guanosine (A>G) point mutations)...
May 8, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28483665/hypoxia-decreases-ros-level-in-human-fibroblasts
#14
G Sgarbi, G Gorini, A Costanzini, S Barbato, G Solaini, A Baracca
We have previously demonstrated that cells adapt to hypoxia using different metabolic reprogramming mechanisms depending on metabolism. We now investigate how the different adapting mechanisms affect reactive oxygen species (ROS) levels, and how ROS levels and cellular metabolism are linked. We show that when skin fibroblasts grew under short-term hypoxia (1% oxygen tension) ROS level markedly decreased (-50%) whatever substrate was available to the cells. Indeed, cellular ROS level linearly and directly decreased with oxygen tension...
May 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28482027/cmr-is-a-redox-responsive-regulator-of-dosr-that-contributes-to-m-tuberculosis-virulence
#15
Laura J Smith, Aleksandra Bochkareva, Matthew D Rolfe, Debbie M Hunt, Christina Kahramanoglou, Yvonne Braun, Angela Rodgers, Alix Blockley, Stephen Coade, Kathryn E A Lougheed, Nor Azian Hafneh, Sarah M Glenn, Jason C Crack, Nick E Le Brun, José W Saldanha, Vadim Makarov, Irene Nobeli, Kristine Arnvig, Galina V Mukamolova, Roger S Buxton, Jeffrey Green
Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression...
May 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28480968/the-influence-of-raav2-mediated-sox2-delivery-into-neonatal-and-adult-human-rpe-cells-a-comparative-study
#16
Razie Ezati, Azadeh Etemadzadeh, Zahra-Soheila Soheili, Shahram Samiei, Ehsan Ranaei Pirmardan, Malihe Davari, Hoda Shams Najafabadi
Cell replacement is a promising therapy for degenerative diseases like age-related macular degeneration (AMD). Since the human retina lacks regeneration capacity, much attention has been directed towards persuading for cells that can differentiate into retinal neurons. In this report we have investigated reprogramming of the human RPE cells and concerned the effect of donor age on the cellular fate as a critical determinant in reprograming competence. We evaluated the effect of SOX2 over-expression in human neonatal and adult RPE cells in cultures...
May 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28478705/rejuvenation-of-cardiac-tissue-developed-from-reprogrammed-aged-somatic-cells
#17
Zhao Cheng, Hong-Ling Peng, Rong Zhang, Xian-Ming Fu, Guang-Sen Zhang
Induced pluripotent stem cells (iPSCs) derived through somatic cell reprogramming have been reported to reset aged somatic cells to a more youthful state, characterized by elongated telomeres, a rearranged mitochondrial network, reduced oxidative stress and restored pluripotency. However, it is still unclear whether the reprogrammed aged somatic cells can function normally as embryonic stem cells (ESCs) during development and be rejuvenated. In the current study, we applied the aggregation technique to investigate whether iPSCs derived from aged somatic cells could develop normally and be rejuvenated...
May 6, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28477135/lentiviral-reprogramming-of-a-t-patient-fibroblasts-to-induced-pluripotent-stem-cells
#18
Sam Nayler, Sergei V Kozlov, Martin F Lavin, Ernst Wolvetang
Reprogramming of cells enables generation of pluripotent stem cells and resulting progeny through directed differentiation, making this technology an invaluable tool for the study of human development and disease. Reprogramming occurs with a wide range of efficiency, a culmination of intrinsic and extrinsic factors including the tissue of origin, the passage number and culture history of the target cells. Another major factor affecting reprogramming is the methodology used and the quality of the reprogramming process itself, including for conventional viral-based approaches viral titer and subsequent viral transduction efficiency, including downstream transgene insertion and stoichiometry...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28473466/antagonistic-regulation-of-cell-cycle-and-differentiation-gene-programs-in-neonatal-cardiomyocytes-by-homologous-mef2-transcription-factors
#19
Cody A Desjardins, Francisco J Naya
Cardiomyocytes acquire their primary specialized function (contraction) prior to exiting the cell cycle. Proliferation and differentiation must be precisely coordinated for proper cardiac morphogenesis. Here, we have investigated the complex transcriptional mechanisms employed by cardiomyocytes to coordinate antagonistic cell cycle and differentiation gene programs through the molecular dissection of the core cardiac transcription factor, MEF2. Knockdown of individual MEF2 proteins, MEF2A, C, and D, in primary neonatal cardiomyocytes resulted in radically distinct and opposite effects on cellular homeostasis and gene regulation...
May 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28472341/in-mammalian-foetal-testes-sox9-regulates-expression-of-its-target-genes-by-binding-to-genomic-regions-with-conserved-signatures
#20
Massilva Rahmoun, Rowena Lavery, Sabine Laurent-Chaballier, Nicolas Bellora, Gayle K Philip, Moïra Rossitto, Aleisha Symon, Eric Pailhoux, Florence Cammas, Jessica Chung, Stefan Bagheri-Fam, Mark Murphy, Vivian Bardwell, David Zarkower, Brigitte Boizet-Bonhoure, Philippe Clair, Vincent R Harley, Francis Poulat
In mammalian embryonic gonads, SOX9 is required for the determination of Sertoli cells that orchestrate testis morphogenesis. To identify genetic networks directly regulated by SOX9, we combined analysis of SOX9-bound chromatin regions from murine and bovine foetal testes with sequencing of RNA samples from mouse testes lacking Sox9. We found that SOX9 controls a conserved genetic programme that involves most of the sex-determining genes. In foetal testes, SOX9 modulates both transcription and directly or indirectly sex-specific differential splicing of its target genes through binding to genomic regions with sequence motifs that are conserved among mammals and that we called 'Sertoli Cell Signature' (SCS)...
May 2, 2017: Nucleic Acids Research
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