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Direct Reprogramming

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https://www.readbyqxmd.com/read/29334121/the-multipotency-to-commitment-transition-mct-in-c-elegans-implications-for-reprogramming-from-cells-to-organs
#1
REVIEW
Erik A Spickard, Pradeep M Joshi, Joel H Rothman
In animal embryos, cells transition from a multipotential state, with the capacity to adopt multiple fates, into an irreversible, committed state of differentiation. This multipotency-to-commitment transition (MCT) is evident from experiments in which cell fate is reprogrammed by transcription factors for cell-type-specific differentiation, as has been observed extensively in C. elegans. Although factors that direct differentiation into each of the three germ layer types cannot generally reprogram cells after the MCT in this animal, transcription factors for endoderm development are able to do so in multiple differentiated cell types...
January 15, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29328434/chemical-conversion-of-human-lung-fibroblasts-into-neuronal-cells
#2
Xiao-Yu Wan, Li-Yun Xu, Bing Li, Qiu-Hong Sun, Qiu-Liang Ji, Dong-Dong Huang, Lan Zhao, Yong-Tao Xiao
It has been previously reported that human embryonic fibroblasts and mouse embryonic fibroblasts can be converted into neuronal cells using chemical agents, along with forced expression specific transcriptional factors. However, the materials required for reprogramming in these approaches presents major technical difficulties and safety concerns. The current study investigated whether a cocktail of small molecules can convert human lung fibroblast cells into neurons. The small molecules valproic acid, CHIR99021, DMH1, Repsox, forskolin, Y‑27632 and SP600125 (VCHRFYS) were used to induce MRC‑5 cells into neuronal cells in vitro...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29327674/insoluble-microenvironment-facilitating-the-generation-and-maintenance-of-pluripotency
#3
Xiaofang Chen, Jiaqi Li, Yan Huang, Peng Liu, Yubo Fan
Induced pluripotent stem cells (iPSCs) hold enormous potential as a tool to generate cells for tissue engineering and regenerative medicine. Since the initial report of iPSCs in 2006, many different methods have been developed in order to enhance the safety and efficiency of this technology. Recent studies indicate that the extracellular signals can promote the production of iPSCs, and even replace the Yamanaka factors. Noticeably, abundant evidences suggest that the insoluble microenvironment, including the culture substrate and neighboring cells, directly regulates the expression of core pluripotency genes and the epigenetic modification of the chromatins, hence impact the reprogramming dynamics...
January 12, 2018: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29327438/establishing-rna-virus-resistance-in-plants-by-harnessing-crispr-immune-system
#4
Tong Zhang, Qiufeng Zheng, Xin Yi, Hong An, Yaling Zhao, Siqi Ma, Guohui Zhou
Recently, CRISPR-Cas (clustered, regularly interspaced short palindromic repeats-CRISPR associated proteins) system has been used to produce plants resistant to DNA virus infections. However, there is no RNA virus control method in plants that uses CRISPR-Cas system to target the viral genome directly. Here we reprogrammed the CRISPR-Cas9 system from Francisella novicida to confer molecular immunity against RNA viruses in Nicotiana benthamiana and Arabidopsis plants. Plants expressing FnCas9 and sgRNA specific for the cucumber mosaic virus (CMV) or tobacco mosaic virus (TMV) exhibited significantly attenuated virus infection symptoms and reduced viral RNA accumulation...
January 11, 2018: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29325037/mediator-complex-component-med13-regulates-zygotic-genome-activation-and-is-required-for-postimplantation-development-in-the-mouse
#5
Yi-Liang Miao, Andrés Gambini, Yingpei Zhang, Elizabeth Padilla-Banks, Wendy N Jefferson, Miranda L Bernhardt, Weichun Huang, Leping Li, Carmen J Williams
Understanding factors that regulate zygotic genome activation (ZGA) is critical for determining how cells are reprogrammed to become totipotent or pluripotent. There is limited information regarding how this process occurs physiologically in early mammalian embryos. Here we identify a mediator complex subunit, MED13, as translated during mouse oocyte maturation and transcribed early from the zygotic genome. Knockdown and conditional knockout approaches demonstrate that MED13 is essential for ZGA in the mouse, in part by regulating expression of the embryo-specific chromatin remodeling complex, esBAF...
January 9, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29319713/adaptable-liquid-crystal-elastomers-with-transesterification-based-bond-exchange-reactions
#6
Drew W Hanzon, Nicholas A Traugutt, Matthew K McBride, Christopher N Bowman, Christopher M Yakacki, Kai Yu
Adaptable liquid crystal elastomers (LCEs) have recently emerged to provide a new and robust method to program monodomain LCE samples. When a constant stress is applied with active bond exchange reactions (BERs), polymer chains and mesogens gradually align in the strain direction. Mesogen alignment is maintained after removing the BER stimulus (e.g. by lowering the temperature) and the programmed LCE samples exhibit free-standing two-way shape switching behavior. Here, a new adaptable main-chain LCE system was developed with thermally induced transesterification BERs...
January 10, 2018: Soft Matter
https://www.readbyqxmd.com/read/29317762/carnitine-palmitoyltransferase-1c-regulates-cancer-cell-senescence-through-mitochondria-associated-metabolic-reprograming
#7
Yongtao Wang, Yixin Chen, Lihuan Guan, Huizheng Zhang, Yaoyao Huang, Caroline H Johnson, Zeming Wu, Frank J Gonzalez, Aiming Yu, Peng Huang, Ying Wang, Shouhui Yang, Pan Chen, Xiaomei Fan, Min Huang, Huichang Bi
Cellular senescence is a fundamental biological process that has profound implications in cancer development and therapeutics, but the underlying mechanisms remain elusive. Here we show that carnitine palmitoyltransferase 1C (CPT1C), an enzyme that catalyzes carnitinylation of fatty acids for transport into mitochondria for β-oxidation, plays a major role in the regulation of cancer cell senescence through mitochondria-associated metabolic reprograming. Metabolomics analysis suggested alterations in mitochondria activity, as revealed by the marked decrease in acylcarnitines in senescent human pancreatic carcinoma PANC-1 cells, indicating low CPT1C activity...
January 9, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29311646/generation-of-functional-dopaminergic-neurons-from-reprogramming-fibroblasts-by-nonviral-based-mesoporous-silica-nanoparticles
#8
Jen-Hsuan Chang, Ping-Hsing Tsai, Kai-Yi Wang, Yu-Ting Wei, Shih-Hwa Chiou, Chung-Yuan Mou
Direct-lineage conversion of the somatic cell by reprogramming, in which mature cells were fully converted into a variety of other cell types bypassing an intermediate pluripotent state, is a promising regenerative medicine approach. Due to the risk of tumorigenesis by viral methods, a non-viral carrier for the delivery of reprogramming factors is very desirable. This study utilized the mesoporous silica nanoparticles (MSNs) as a non-viral delivery system for transduction of the three key factors to achieve conversion of mouse fibroblasts (MFs) into functional dopaminergic neuron-like cells (denoted as fDA-neurons)...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29309622/strigolactones-cross-the-kingdoms-plants-fungi-and-bacteria-in-the-arbuscular-mycorrhizal-symbiosis
#9
Luisa Lanfranco, Valentina Fiorilli, Francesco Venice, Paola Bonfante
Strigolactones (SLs) first evolved as regulators of simple developmental processes in very ancient plant lineages, and then assumed new roles to sustain the increasing biological complexity of land plants. Their versatility is also shown by the fact that during evolution they have been exploited, once released in the rhizosphere, as a communication system towards plant-interacting organisms even belonging to different kingdoms. Here, we reviewed the impact of SLs on soil microbes, paying particular attention to arbuscular mycorrhizal fungi (AMF)...
December 22, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29309130/reprograming-the-replisome-of-a-semisynthetic-organism-for-the-expansion-of-the-genetic-alphabet
#10
Michael P Ledbetter, Rebekah J Karadeema, Floyd E Romesberg
Semisynthetic organisms (SSOs) created from Escherichia coli can replicate a plasmid containing an unnatural base pair (UBP) formed between the synthetic nucleosides dNaM and dTPT3 (dNaM-dTPT3) when the corresponding unnatural triphosphates are imported via expression of a nucleoside triphosphate transporter. The UBP can also be transcribed and used to translate proteins containing unnatural amino acids. However, UBPs are not well retained in all sequences, limiting the information that can be encoded, and are invariably lost upon extended growth...
January 8, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29301845/elixir-of-life-thwarting-aging-with-regenerative-reprogramming
#11
REVIEW
Ergin Beyret, Paloma Martinez Redondo, Aida Platero Luengo, Juan Carlos Izpisua Belmonte
All living beings undergo systemic physiological decline after ontogeny, characterized as aging. Modern medicine has increased the life expectancy, yet this has created an aged society that has more predisposition to degenerative disorders. Therefore, novel interventions that aim to extend the healthspan in parallel to the life span are needed. Regeneration ability of living beings maintains their biological integrity and thus is the major leverage against aging. However, mammalian regeneration capacity is low and further declines during aging...
January 5, 2018: Circulation Research
https://www.readbyqxmd.com/read/29301628/platelet-derived-mrp-14-induces-monocyte-activation-in-patients-with-symptomatic-peripheral-artery-disease
#12
Rebecca Dann, Tarik Hadi, Emilie Montenont, Ludovic Boytard, Dornaszadat Alebrahim, Jordyn Feinstein, Nicole Allen, Russell Simon, Krista Barone, Kunihiro Uryu, Yu Guo, Caron Rockman, Bhama Ramkhelawon, Jeffrey S Berger
BACKGROUND: Peripheral artery disease (PAD), a diffuse manifestation of atherothrombosis, is a major cardiovascular threat. Although platelets are primary mediators of atherothrombosis, their role in the pathogenesis of PAD remains unclear. OBJECTIVES: The authors sought to investigate the role of platelets in a cohort of symptomatic PAD. METHODS: The authors profiled platelet activity, mRNA, and effector roles in patients with symptomatic PAD and in healthy controls...
January 2, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29300726/regulation-of-circadian-clock-transcriptional-output-by-clock-bmal1
#13
Alexandra J Trott, Jerome S Menet
The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of 15% of the transcriptome and control the daily regulation of biological functions. The recent characterization of CLOCK:BMAL1 cistrome revealed that although CLOCK:BMAL1 binds synchronously to all of its target genes, its transcriptional output is highly heterogeneous. By performing a meta-analysis of several independent genome-wide datasets, we found that the binding of other transcription factors at CLOCK:BMAL1 enhancers likely contribute to the heterogeneity of CLOCK:BMAL1 transcriptional output...
January 4, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29296233/srebp-2-driven-transcriptional-activation-of-human-snd1-oncogene
#14
Sandra Armengol, Enara Arretxe, Leire Enzunza, Irati Llorente, Unai Mendibil, Hiart Navarro-Imaz, Begoña Ochoa, Yolanda Chico, María José Martínez
Upregulation of Staphylococcal nuclease and tudor domain containing 1 (SND1) is linked to cancer progression and metastatic spread. Increasing evidence indicates that SND1 plays a role in lipid homeostasis. Recently, it has been shown that SND1-overexpressing hepatocellular carcinoma cells present an increased de novo cholesterol synthesis and cholesteryl ester accumulation. Here we reveal that SND1 oncogene is a novel target for SREBPs. Exposure of HepG2 cells to the cholesterol-lowering drug simvastatin or to a lipoprotein-deficient medium triggers SREBP-2 activation and increases SND1 promoter activity and transcript levels...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290953/viral-e6-e7-oncogene-and-cellular-hexokinase-2-expression-in-hpv-positive-cancer-cell-lines
#15
Karin Hoppe-Seyler, Anja Honegger, Felicitas Bossler, Jasmin Sponagel, Julia Bulkescher, Claudia Lohrey, Felix Hoppe-Seyler
Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. Cancer cells typically exhibit metabolic alterations which support their malignant growth. These include an enhanced rate of aerobic glycolysis ('Warburg effect') which in cancer cells is often linked to an increased expression of the rate-limiting glycolytic enzyme Hexokinase 2 (HK2). Intriguingly, recent studies indicate that the HPV E6/E7 oncogenes cause the metabolic reprogramming in HPV-positive cancer cells by directly upregulating HK2 expression...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290790/changes-in-the-microarchitecture-of-the-pancreatic-cancer-stroma-are-linked-to-neutrophil-dependent-reprogramming-of-stellate-cells-and-reflected-by-diffusion-weighted-magnetic-resonance-imaging
#16
Philipp Mayer, Christine Dinkic, Ralf Jesenofsky, Miriam Klauss, Peter Schirmacher, Ulrike Dapunt, Thilo Hackert, Florian Uhle, G Maria Hänsch, Matthias M Gaida
In pancreatic cancer (PDAC) intratumor infiltration of polymorphonuclear neutrophils (PMN) is associated with histologically apparent alterations of the tumor growth pattern. The aim of this study was to examine possible associations between PMN infiltration, tumor microarchitecture, and water diffusivity in diffusion-weighted magnetic resonance imaging (DW-MRI), and to further asses the underlying mechanisms. Methods: DW-MRI was performed in 33 PDAC patients prior to surgery. In parallel, tissue specimen were examined histologically for growth pattern, azurocidin-positive PMN infiltrates, and the presence of alpha-smooth muscle actin (α-SMA) and metalloproteinase 9 (MMP9)-positive myofibroblastic cells...
2018: Theranostics
https://www.readbyqxmd.com/read/29282070/9-4%C3%A2-t-small-animal-mri-using-clinical-components-for-direct-translational-studies
#17
Jörg Felder, A Avdo Celik, Chang-Hoon Choi, Stefan Schwan, N Jon Shah
BACKGROUND: Magnetic resonance is a major preclinical and clinical imaging modality ideally suited for longitudinal studies, e.g. in pharmacological developments. The lack of a proven platform that maintains an identical imaging protocol between preclinical and clinical platforms is solved with the construction of an animal scanner based on clinical hard- and software. METHODS: A small animal magnet and gradient system were connected to a clinical MR system. Several hardware components were either modified or built in-house to achieve compatibility...
December 28, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29281830/oncogenic-myc-activates-a-feedforward-regulatory-loop-promoting-essential-amino-acid-metabolism-and-tumorigenesis
#18
Ming Yue, Jue Jiang, Peng Gao, Hudan Liu, Guoliang Qing
Most tumor cells exhibit obligatory demands for essential amino acids (EAAs), but the regulatory mechanisms whereby tumor cells take up EAAs and EAAs promote malignant transformation remain to be determined. Here, we show that oncogenic MYC, solute carrier family (SLC) 7 member 5 (SLC7A5), and SLC43A1 constitute a feedforward activation loop to promote EAA transport and tumorigenesis. MYC selectively activates Slc7a5 and Slc43a1 transcription through direct binding to specific E box elements within both genes, enabling effective EAA import...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29276141/direct-in%C3%A2-vivo-reprogramming-with-sendai-virus-vectors-improves-cardiac-function-after-myocardial-infarction
#19
Kazutaka Miyamoto, Mizuha Akiyama, Fumiya Tamura, Mari Isomi, Hiroyuki Yamakawa, Taketaro Sadahiro, Naoto Muraoka, Hidenori Kojima, Sho Haginiwa, Shota Kurotsu, Hidenori Tani, Li Wang, Li Qian, Makoto Inoue, Yoshinori Ide, Junko Kurokawa, Tsunehisa Yamamoto, Tomohisa Seki, Ryo Aeba, Hiroyuki Yamagishi, Keiichi Fukuda, Masaki Ieda
Direct cardiac reprogramming holds great promise for regenerative medicine. We previously generated directly reprogrammed induced cardiomyocyte-like cells (iCMs) by overexpression of Gata4, Mef2c, and Tbx5 (GMT) using retrovirus vectors. However, integrating vectors pose risks associated with insertional mutagenesis and disruption of gene expression and are inefficient. Here, we show that Sendai virus (SeV) vectors expressing cardiac reprogramming factors efficiently and rapidly reprogram both mouse and human fibroblasts into integration-free iCMs via robust transgene expression...
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29260008/functional-validation-and-expression-analysis-of-myotubes-converted-from-skin-fibroblasts-using-a-simple-direct-reprogramming-strategy
#20
Fukuko Horio, Hidetoshi Sakurai, Yutaka Ohsawa, Shiho Nakano, Makoto Matsukura, Isao Fujii
Previously, we reported that MyoD, a master gene for myogenic cells, could efficiently convert primary skin fibroblasts into myoblasts and myotubes, thereby effecting direct reprogramming. In this study, we further demonstrated that MyoD-expressing primary fibroblasts displayed rapid movement in culture, with a movement velocity that was significantly faster, almost four times, than mouse primary myoblasts. MyoD-transduced cells obtained the characteristics of Ca2 + release and electrically-stimulated contraction, which was comparable to C2C12 myotubes, suggesting that the essential features of muscle were observed in the transduced cells...
March 2017: ENeurologicalSci
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