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Direct Reprogramming

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https://www.readbyqxmd.com/read/29156730/generation-of-patient-specific-human-neural-stem-cells-from-niemann-pick-disease-type-c-patient-derived-fibroblasts
#1
Eun-Ah Sung, Kyung-Rok Yu, Ji-Hee Shin, Yoojin Seo, Hyung-Sik Kim, Myung Guen Koog, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Tae-Hoon Shin, Jin Young Lee, Seunghee Lee, Tae-Wook Kang, Soon Won Choi, Kyung-Sun Kang
Niemann-Pick disease type C (NPC) is a neurodegenerative and lysosomal lipid storage disorder, characterized by the abnormal accumulation of unesterified cholesterol and glycolipids, which is caused by mutations in the NPC1 genes. Here, we report the generation of human induced neural stem cells from NPC patient-derived fibroblasts (NPC-iNSCs) using only two reprogramming factors SOX2 and HMGA2 without going through the pluripotent state. NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155818/snail1-mediated-downregulation-of-foxa-proteins-facilitates-the-inactivation-of-transcriptional-enhancer-elements-at-key-epithelial-genes-in-colorectal-cancer-cells
#2
Sabine Jägle, Hauke Busch, Vivien Freihen, Sven Beyes, Monika Schrempp, Melanie Boerries, Andreas Hecht
Phenotypic conversion of tumor cells through epithelial-mesenchymal transition (EMT) requires massive gene expression changes. How these are brought about is not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anticorrelated in transcriptomes of colorectal tumors and cell lines...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29154162/epigenetic-reprogramming-in-metabolic-disorders-nutritional-factors-and-beyond
#3
REVIEW
Zhiyong Cheng, Louise Zheng, Fabio A Almeida
Environmental factors (e.g., malnutrition and physical inactivity) contribute largely to metabolic disorders including obesity, type 2 diabetes, cardiometabolic disease and nonalcoholic fatty liver diseases. The abnormalities in metabolic activity and pathways have been increasingly associated with altered DNA methylation, histone modification and noncoding RNAs, whereas lifestyle interventions targeting diet and physical activity can reverse the epigenetic and metabolic changes. Here we review recent evidence primarily from human studies that links DNA methylation reprogramming to metabolic derangements or improvements, with a focus on cross-tissue (e...
October 23, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29151989/human-induced-pluripotent-stem-cells-and-the-modelling-of-alzheimer-s-disease-the-human-brain-outside-the-dish
#4
REVIEW
Godwin Tong, Pablo Izquierdo, Rana Arham Raashid
Background: Neurodegenerative diseases like Alzheimer's Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments. Summary: With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth...
2017: Open Neurology Journal
https://www.readbyqxmd.com/read/29150086/the-ex-vivo-toll-like-receptor-7-tolerance-induction-in-donor-lymphocytes-prevents-murine-acute-graft-versus-host-disease
#5
Nikolaos Zogas, Garyfalia Karponi, Fotios Iordanidis, Stylianos Malasidis, Vasilios Paraskevas, Anastasia Papadopoulou, Zaharias George Scouras, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND AIMS: Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation, mediated by alloreactive donor T cells. Toll-like receptors (TLRs), a family of conserved pattern-recognition receptors (PRRs), represent key players in donors' T-cell activation during aGVHD; however, a regulatory, tolerogenic role for certain TLRs has been recognized in a different context. We investigated whether the ex vivo-induced TLR-2,-4,-7 tolerance in donor cells could prevent alloreactivity in a mismatched transplantation model...
November 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#6
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29145928/note-of-clarification-potential-risks-to-offspring-of-intrauterine-exposure-to-maternal-age-related-obstetric-complications
#7
Juan J Tarín, Miguel A García-Pérez, Antonio Cano
Several hypotheses have been proposed to explain the negative effects of delayed motherhood on an offspring's morbidity later in life. However, these hypotheses are not supported by clinical and epidemiological evidence. Because advanced maternal age is associated with increased risk of obstetric complications, the aim of the present study was to ascertain whether the negative effects on offspring of intrauterine exposure to maternal age-related obstetric complications may explain the reported negative effects of delayed motherhood on offspring...
August 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29143810/next-generation-pacemakers-from-small-devices-to-biological-pacemakers
#8
REVIEW
Eugenio Cingolani, Joshua I Goldhaber, Eduardo Marbán
Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator...
November 16, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29138396/polo-like-kinase-1-coordinates-biosynthesis-during-cell-cycle-progression-by-directly-activating-pentose-phosphate-pathway
#9
Xiaoyu Ma, Lin Wang, De Huang, Yunyan Li, Dongdong Yang, Tingting Li, Fudong Li, Linchong Sun, Haoran Wei, Kun He, Fazhi Yu, Debiao Zhao, Lan Hu, Songge Xing, Zhaoji Liu, Kui Li, Jing Guo, Zhenye Yang, Xin Pan, Ailing Li, Yunyu Shi, Junfeng Wang, Ping Gao, Huafeng Zhang
Two hallmarks for cancer cells are the accelerated cell cycle progression as well as the altered metabolism, however, how these changes are coordinated to optimize the growth advantage for cancer cells are still poorly understood. Here we identify that Polo-like kinase 1 (Plk1), a key regulator for cell mitosis, plays a critical role for biosynthesis in cancer cells through activating pentose phosphate pathway (PPP). We find that Plk1 interacts with and directly phosphorylates glucose-6-phosphate dehydrogenase (G6PD)...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29137640/direct-reprogramming-of-mouse-fibroblasts-into-neural-cells-via-porphyra-yezoensis-polysaccharide-based-high-efficient-gene-co-delivery
#10
Qingtong Yu, Jingjing Chen, Wenwen Deng, Xia Cao, Yan Wang, Jie Zhou, Wenqian Xu, Pan Du, Qiang Wang, Jiangnan Yu, Ximing Xu
BACKGROUND: The cell source for transplantation therapy is always a prerequisite question to be solved in clinical applications. Neural cells are considered non-regenerable, which highly restrict their application in the treatment for nerve injury. Therefore, neural trans-differentiation based on gene transfection provides a new solution to this issue. Compared to viral strategy, non-viral gene delivery systems are considered as a more promising way to achieve this aim. This study centers on a novel application of Porphyra yezoensis polysaccharide as a non-viral gene carrier for the neural trans-differentiation of mouse fibroblasts...
November 14, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29130995/lncrna-uca1-promotes-mitochondrial-function-of-bladder-cancer-via-the-mir-195-arl2-signaling-pathway
#11
Hui-Jin Li, Xiao-Min Sun, Zheng-Kun Li, Qian-Wen Yin, Huan Pang, Jing-Jing Pan, Xu Li, Wei Chen
BACKGROUND/AIMS: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. METHODS: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells...
November 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130642/dual-inhibition-of-dnmts-and-ezh2-can-overcome-both-intrinsic-and-acquired-resistance-of-myeloma-cells-to-imids-in-a-cereblon-independent-manner
#12
Konstantinos Dimopoulos, Alexandra Søgaard Helbo, Helga Fibiger Munch-Petersen, Lene Sjö, Jesper Christensen, Lasse Sommer Kristensen, Fazila Asmar, Emil Hermansen, Casey O'Connel, Peter Gimsing, Gangning Liang, Kirsten Grønbaek
Thalidomide and its derivatives, lenalidomide and pomalidomide (also known as IMiDs), have significantly changed the treatment landscape of multiple myeloma, and the recent discovery of cereblon (CRBN) as their direct biological target has led to a deeper understanding of their complex mechanism of action. In an effort to comprehend the precise mechanisms behind the development of IMiD resistance and examine whether it is potentially reversible, we established lenalidomide- (-LR) and pomalidomide-resistant (-PR) human myeloma cell lines from two IMiD-sensitive cell lines, OPM2 and NCI-H929, by continuous culture in the presence of lenalidomide or pomalidomide for 4-6 months, until acquirement of stable resistance...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29121773/systems-biology-approaches-to-redox-metabolism-in-stress-and-disease-states
#13
Rui-Sheng Wang, William M Oldham, Bradley A Maron, Joseph Loscalzo
Significance All cellular metabolic processes are tied to the cellular redox environment. Therefore, maintaining redox homeostasis is critically important for normal cell function. Indeed, redox stress contributes to the pathobiology of many human diseases. The cellular redox response system is composed of numerous interconnected components including free radicals, redox couples, protein thiols, enzymes, metabolites, and transcription factors. Moreover, interactions between and among these factors are regulated in time and space...
November 9, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29116745/nanotopographic-regulation-of-human-mesenchymal-stem-cell-osteogenesis
#14
Weiyi Qian, Lanqi Gong, Xin Cui, Zijing Zhang, Apratim Bajpai, Chao Liu, Alesha B Castillo, Jeremy C M Teo, Weiqiang Chen
Mesenchymal stem cell (MSC) differentiation can be manipulated by nanotopographic interface providing a unique strategy to engineering stem cell therapy and circumventing complex cellular reprogramming. However, our understanding of the nanotopographic-mechanosensitive properties of MSCs and the underlying biophysical linkage of the nanotopography-engineered stem cell to directed commitment remains elusive. Here, we show that osteogenic differentiation of human MSCs (hMSCs) can be largely promoted using our nanoengineered topographic glass substrates in the absence of dexamethasone, a key exogenous factor for osteogenesis induction...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29116664/unraveling-the-biology-of-bipolar-disorder-using-induced-pluripotent-stem-derived-neurons
#15
REVIEW
Nathaniel D Miller, John R Kelsoe
OBJECTIVES: Bipolar disorder has been studied from numerous angles, from pathological studies to large-scale genomic studies, overall making moderate gains toward an understanding of the disorder. With the advancement of induced pluripotent stem (iPS) cell technology, in vitro models based on patient samples are now available that inherently incorporate the complex genetic variants that largely are the basis for this disorder. A number of groups are starting to apply iPS technology to the study of bipolar disorder...
November 8, 2017: Bipolar Disorders
https://www.readbyqxmd.com/read/29115987/cancer-cell-soluble-factors-reprogram-mesenchymal-stromal-cells-to-slow-cycling-chemoresistant-cells-with-a-more-stem-like-state
#16
Ahmed El-Badawy, Mohamed A Ghoneim, Mahmoud M Gabr, Radwa Ayman Salah, Ihab K Mohamed, Marwa Amer, Nagwa El-Badri
BACKGROUND: Mesenchymal stem cells (MSCs) play different roles in modulating tumor progression, growth, and metastasis. MSCs are recruited to the tumor site in large numbers and subsequently have an important microenvironmental role in modulating tumor progression and drug sensitivity. However, the effect of the tumor microenvironment on MSC plasticity remains poorly understood. Herein, we report a paracrine effect of cancer cells, in which they secrete soluble factors that promote a more stem-like state in bone marrow mesenchymal stem cells (BM-MSCs)...
November 7, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29114178/cancer-metabolism-and-tumor-heterogeneity-imaging-perspectives-using-mr-imaging-and-spectroscopy
#17
REVIEW
Gigin Lin, Kayvan R Keshari, Jae Mo Park
Cancer cells reprogram their metabolism to maintain viability via genetic mutations and epigenetic alterations, expressing overall dynamic heterogeneity. The complex relaxation mechanisms of nuclear spins provide unique and convertible tissue contrasts, making magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) pertinent imaging tools in both clinics and research. In this review, we summarized MR methods that visualize tumor characteristics and its metabolic phenotypes on an anatomical, microvascular, microstructural, microenvironmental, and metabolomics scale...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29114069/bag3-directly-stabilizes-hexokinase-2-mrna-and-promotes-aerobic-glycolysis-in-pancreatic-cancer-cells
#18
Ming-Xin An, Si Li, Han-Bing Yao, Chao Li, Jia-Mei Wang, Jia Sun, Xin-Yu Li, Xiao-Na Meng, Hua-Qin Wang
Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29109268/syntenin-mediates-src-function-in-exosomal-cell-to-cell-communication
#19
Naga Sailaja Imjeti, Kerstin Menck, Antonio Luis Egea-Jimenez, Celine Lecointre, Frederique Lembo, Habib Bouguenina, Ali Badache, Rania Ghossoub, Guido David, Serge Roche, Pascale Zimmermann
The cytoplasmic tyrosine kinase SRC controls cell growth, proliferation, adhesion, and motility. The current view is that SRC acts primarily downstream of cell-surface receptors to control intracellular signaling cascades. Here we reveal that SRC functions in cell-to-cell communication by controlling the biogenesis and the activity of exosomes. Exosomes are viral-like particles from endosomal origin that can reprogram recipient cells. By gain- and loss-of-function studies, we establish that SRC stimulates the secretion of exosomes having promigratory activity on endothelial cells and that syntenin is mandatory for SRC exosomal function...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29104580/hexanoic-acid-treatment-prevents-systemic-mnsv-movement-in-cucumis-melo-plants-by-priming-callose-deposition-correlating-sa-and-opda-accumulation
#20
Emma Fernández-Crespo, Jose A Navarro, Marta Serra-Soriano, Iván Finiti, Pilar García-Agustín, Vicente Pallás, Carmen González-Bosch
Unlike fungal and bacterial diseases, no direct method is available to control viral diseases. The use of resistance-inducing compounds can be an alternative strategy for plant viruses. Here we studied the basal response of melon to Melon necrotic spot virus (MNSV) and demonstrated the efficacy of hexanoic acid (Hx) priming, which prevents the virus from systemically spreading. We analysed callose deposition and the hormonal profile and gene expression at the whole plant level. This allowed us to determine hormonal homeostasis in the melon roots, cotyledons, hypocotyls, stems and leaves involved in basal and hexanoic acid-induced resistance (Hx-IR) to MNSV...
2017: Frontiers in Plant Science
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