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Young-Dan Cho, Hyun-Mo Ryoo
In regenerative medicine, growing cells or tissues in the laboratory is necessary when damaged cells can not heal by themselves. Acquisition of the required cells from the patient's own cells or tissues is an ideal option without additive side effects. In this context, cell reprogramming methods, including the use of induced pluripotent stem cells (iPSCs) and trans-differentiation, have been widely studied in regenerative research. Both approaches have advantages and disadvantages, and the possibility of de-differentiation because of the epigenetic memory of iPSCs has strengthened the need for controlling the epigenetic background for successful cell reprogramming...
February 2018: Journal of Bone Metabolism
Pau B Esparza-Moltó, José M Cuezva
Cancer cells reprogram energy metabolism by boosting aerobic glycolysis as a main pathway for the provision of metabolic energy and of precursors for anabolic purposes. Accordingly, the relative expression of the catalytic subunit of the mitochondrial H+ -ATP synthase-the core hub of oxidative phosphorylation-is downregulated in human carcinomas when compared with its expression in normal tissues. Moreover, some prevalent carcinomas also upregulate the ATPase inhibitory factor 1 (IF1), which is the physiological inhibitor of the H+ -ATP synthase...
2018: Frontiers in Oncology
Syeda Nayab Fatima Abidi, Rachel K Smith-Bolton
The imaginal discs of the genetically tractable model organism Drosophila melanogaster have been used to study cell-fate specification and plasticity, including homeotic changes and regeneration-induced transdetermination. The identity of the reprogramming mechanisms that induce plasticity has been of great interest in the field. Here we identify a change from antennal fate to eye fate induced by a Distal-less-GAL4 (DllGAL4) P-element insertion that is a mutant allele of Dll and expresses GAL4 in the antennal imaginal disc...
March 21, 2018: Scientific Reports
Lucie Bacakova, Jana Zarubova, Martina Travnickova, Jana Musilkova, Julia Pajorova, Petr Slepicka, Nikola Slepickova Kasalkova, Vaclav Svorcik, Zdenka Kolska, Hooman Motarjemi, Martin Molitor
Stem cells can be defined as units of biological organization that are responsible for the development and the regeneration of organ and tissue systems. They are able to renew their populations and to differentiate into multiple cell lineages. Therefore, these cells have great potential in advanced tissue engineering and cell therapies. When seeded on synthetic or nature-derived scaffolds in vitro, stem cells can be differentiated towards the desired phenotype by an appropriate composition, by an appropriate architecture, and by appropriate physicochemical and mechanical properties of the scaffolds, particularly if the scaffold properties are combined with a suitable composition of cell culture media, and with suitable mechanical, electrical or magnetic stimulation...
March 18, 2018: Biotechnology Advances
Jiajie Tu, Geng Tian, Hoi-Hung Cheung, Wei Wei, Tin-Lap Lee
BACKGROUND: The regulatory role of long noncoding RNAs (lncRNAs) have been partially proved in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). METHODS: In the current study, we investigated mouse ESC (mESC) self-renewal, differentiation, and proliferation in vitro by knocking down a lncRNA, growth arrest specific 5 (Gas5). A series of related indicators were examined by cell counting kit-8 (CCK-8) assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blot, alkaline phosphatase staining, propidium iodide (PI) staining, Annexin V staining, competition growth assay, immunofluorescence, and chromatin immunoprecipitation (ChIP)-qPCR...
March 21, 2018: Stem Cell Research & Therapy
Christine T Styles, Kostas Paschos, Robert E White, Paul J Farrell
The Epstein-Barr nuclear antigen 3 (EBNA3) family of proteins, comprising EBNA3A, EBNA3B, and EBNA3C, play pivotal roles in the asymptomatic persistence and life-long latency of Epstein-Barr virus (EBV) in the worldwide human population. EBNA3-mediated transcriptional reprogramming of numerous host cell genes promotes in vitro B cell transformation and EBV persistence in vivo. Despite structural and sequence similarities, and evidence of substantial cooperative activity between the EBNA3 proteins, they perform quite different, often opposing functions...
March 17, 2018: Pathogens
Wei Zhang, Guihai Feng, Libin Wang, Fei Teng, Liu Wang, Wei Li, Ying Zhang, Qi Zhou
The generation of induced pluripotent stem cells (iPSCs) offers a great opportunity in research and regenerative medicine. The current poor efficiency and incomplete mechanistic understanding of the reprogramming process hampers the clinical application of iPSCs. MeCP2 connects histone modification and DNA methylation, which are key changes of somatic cell reprogramming. However, the role of MeCP2 in cell reprogramming has not been examined. In this study, we found that MeCP2 deficiency enhanced reprogramming efficiency and stimulated cell proliferation through regulating cell cycle protein expression in the early stage of reprogramming...
March 19, 2018: Journal of Molecular Cell Biology
Hirofumi Noguchi, Chika Miyagi-Shiohira, Yoshiki Nakashima
Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. The pattern of expressed genes, DNA methylation, and covalent histone modifications in iPS cells are very similar to those in ES cells. However, it has recently been shown that, following the reprogramming of mouse/human iPS cells, epigenetic memory is inherited from the parental cells. These findings suggest that the phenotype of iPS cells may be influenced by their cells of origin and that their skewed differentiation potential may prove useful in the generation of differentiated cell types that are currently difficult to produce from ES/iPS cells for the treatment of human diseases...
March 21, 2018: International Journal of Molecular Sciences
Brian B Silver, Celeste M Nelson
Cancer is a complex, heterogeneous group of diseases that can develop through many routes. Broad treatments such as chemotherapy destroy healthy cells in addition to cancerous ones, but more refined strategies that target specific pathways are usually only effective for a limited number of cancer types. This is largely due to the multitude of physiological variables that differ between cells and their surroundings. It is therefore important to understand how nature coordinates these variables into concerted regulation of growth at the tissue scale...
2018: Frontiers in Cell and Developmental Biology
Katharine H Wrighton
No abstract text is available yet for this article.
March 21, 2018: Nature Reviews. Molecular Cell Biology
Ying Chen, Zetian Shen, Yingru Zhi, Hao Zhou, Kai Zhang, Ting Wang, Bing Feng, Yitian Chen, Haizhu Song, Rui Wang, Xiaoyuan Chu
Radiotherapy plays a limited role in the treatment of hepatocellular carcinoma (HCC) due to the development of resistance. Therefore, further investigation of underlying mechanisms involved in HCC radioresistance is warranted. Increasing evidence shows that long non-coding RNAs (linc-RNAs) are involved in the pathology of various tumors, including HCC. Previously, we have shown that long noncoding RNA regulator of reprogramming (linc-ROR) promotes HCC metastasis via induction of epithelial-mesenchymal transition (EMT)...
March 17, 2018: Archives of Biochemistry and Biophysics
Srijaya Thekkeparambil Chandrabose, Sandhya Sriram, Subha Subramanian, Shanshan Cheng, Wee Kiat Ong, Steve Rozen, Noor Hayaty Abu Kasim, Shigeki Sugii
BACKGROUND: While a shift towards non-viral and animal component-free methods of generating induced pluripotent stem (iPS) cells is preferred for safer clinical applications, there is still a shortage of reliable cell sources and protocols for efficient reprogramming. METHODS: Here, we show a robust episomal and xeno-free reprogramming strategy for human iPS generation from dental pulp stem cells (DPSCs) which renders good efficiency (0.19%) over a short time frame (13-18 days)...
March 20, 2018: Stem Cell Research & Therapy
Francesca Andriani, Maria Teresa Majorini, Miguel Mano, Elena Landoni, Rosalba Miceli, Federica Facchinetti, Mavis Mensah, Enrico Fontanella, Matteo Dugo, Mauro Giacca, Ugo Pastorino, Gabriella Sozzi, Domenico Delia, Luca Roz, Daniele Lecis
BACKGROUND: Fibroblasts are crucial mediators of tumor-stroma cross-talk through synthesis and remodeling of the extracellular matrix and production of multiple soluble factors. Nonetheless, little is still known about specific determinants of fibroblast pro-tumorigenic activity in lung cancer. Here, we aimed at understanding the role of miRNAs, which are often altered in stromal cells, in reprogramming fibroblasts towards a tumor-supporting phenotype. METHODS: We employed a co-culture-based high-throughput screening to identify specific miRNAs modulating the pro-tumorigenic potential of lung fibroblasts...
March 20, 2018: Journal of Hematology & Oncology
Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
Gao-Min Liu, Yao-Ming Zhang
Cancer is a leading cause of death in both developed and developing countries. Metabolic reprogramming is an emerging hallmark of cancer. Glucose homeostasis is reciprocally controlled by the catabolic glycolysis and anabolic gluconeogenesis pathways. Previous studies have mainly focused on catabolic glycolysis, but recently, FBPase, a rate-limiting enzyme in gluconeogenesis, was found to play critical roles in tumour initiation and progression in several cancer types. Here, we review recent ideas and discoveries that illustrate the clinical significance of FBPase expression in various cancers, the mechanism through which FBPase influences cancer, and the mechanism of FBPase silencing...
2018: Cancer Cell International
Anniina Vihervaara, Fabiana M Duarte, John T Lis
Proteotoxic stress, that is, stress caused by protein misfolding and aggregation, triggers the rapid and global reprogramming of transcription at genes and enhancers. Genome-wide assays that track transcriptionally engaged RNA polymerase II (Pol II) at nucleotide resolution have provided key insights into the underlying molecular mechanisms that regulate transcriptional responses to stress. In addition, recent kinetic analyses of transcriptional control under heat stress have shown how cells 'prewire' and rapidly execute genome-wide changes in transcription while concurrently becoming poised for recovery...
March 19, 2018: Nature Reviews. Genetics
Mistianne Feeney, Maike Kittelmann, Rima Menassa, Chris Hawes, Lorenzo Frigerio
Protein storage vacuoles (PSV) are the main repository of protein in dicotyledonous seeds, but little is known about the origins of these transient organelles. PSV are hypothesised to either arise de novo or to originate from the pre-existing embryonic vacuole (EV) during seed maturation. Here, we tested these hypotheses by studying PSV formation in Arabidopsis (Arabidopsis thaliana) embryos at different stages of seed maturation and recapitulated this process in Arabidopsis leaves reprogrammed to an embryogenic fate by inducing expression of the LEAFY COTYLEDON2 transcription factor...
March 19, 2018: Plant Physiology
Monia Cito, Silvia Pellegrini, Lorenzo Piemonti, Valeria Sordi
The experience in the field of islet transplantation shows that it is possible to replace β cells in a patient with type 1 diabetes (T1D), but this cell therapy is limited by the scarcity of organ donors and by the danger associated to the immunosuppressive drugs. Stem cell therapy is becoming a concrete opportunity to treat various diseases. In particular, for a disease like T1D, caused by the loss of a single specific cell type that does not need to be transplanted back in its originating site to perform its function, a stem cell-based cell replacement therapy seems to be the ideal cure...
March 2018: Endocrine Connections
Aarne Fleischer, Iván M Lorenzo, Esther Palomino, Trond Aasen, Fernando Gómez, Miguel Servera, Víctor J Asensio, Víctor Gálvez, Juan Carlos Izpisúa-Belmonte, Daniel Bachiller
Cystic Fibrosis (CF) is a monogenic, lethal disease caused by mutations in the cystic fibrosis transmembrane conductance (CFTR) gene. Here we report the production of CF-iPS cell lines from two different p.F508del homozygous female patients (Table 1). Two different primary cell types, skin fibroblasts and keratinocytes, were transfected with retroviral cocktails containing four: c-MYC, KLF4, OCT4 and SOX2 (MKOS) or three: KLF4, OCT4 and SOX2 (KOS) reprogramming factors. Two fibroblast-derived MKOS lines are described in the main text...
March 11, 2018: Stem Cell Research
Lan Huang, Huaxi Xu, Guangyong Peng
Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival, proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment. A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments. Toll-like receptors (TLRs) have recently been recognized as critical factors involved in tumor pathogenesis, regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells...
March 19, 2018: Cellular & Molecular Immunology
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