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Cellular Reprogramming

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https://www.readbyqxmd.com/read/28099929/modeling-the-phenotype-of-spinal-muscular-atrophy-by-the-direct-conversion-of-human-fibroblasts-to-motor-neurons
#1
Qi-Jie Zhang, Jin-Jing Li, Xiang Lin, Ying-Qian Lu, Xin-Xin Guo, En-Lin Dong, Miao Zhao, Jin He, Ning Wang, Wan-Jin Chen
Spinal muscular atrophy (SMA) is a lethal autosomal recessive neurological disease characterized by selective degeneration of motor neurons in the spinal cord. In recent years, the development of cellular reprogramming technology has provided an alternative and effective method for obtaining patient-specific neurons in vitro. In the present study, we applied this technology to the field of SMA to acquire patient-specific induced motor neurons that were directly converted from fibroblasts via the forced expression of 8 defined transcription factors...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099079/lymphangioleiomyomatosis-a-monogenic-model-of-malignancy
#2
Vera P Krymskaya, Francis X McCormack
Lymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All pulmonary structures become infiltrated with benign-appearing spindle and epithelioid cells (LAM cells) that express smooth-muscle and melanocyte-lineage markers, harbor mTOR-activating mutations in tuberous sclerosis complex (TSC) genes, and recruit abundant stromal cells. Elaboration of lymphangiogenic growth factors and matrix remodeling enzymes by LAM cells enables their access to lymphatic channels and likely drives the cystic lung remodeling that often culminates in respiratory failure...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/28095779/poly-adp-ribose-polymerase-inhibitors-activate-the-p53-signaling-pathway-in-neural-stem-progenitor-cells
#3
Akiko Okuda, Suguru Kurokawa, Masanori Takehashi, Aika Maeda, Katsuya Fukuda, Yukari Kubo, Hyuma Nogusa, Tomoka Takatani-Nakase, Shujiro Okuda, Kunihiro Ueda, Seigo Tanaka
BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP-1), which catalyzes poly(ADP-ribosyl)ation of proteins by using NAD(+) as a substrate, plays a key role in several nuclear events, including DNA repair, replication, and transcription. Recently, PARP-1 was reported to participate in the somatic cell reprogramming process. Previously, we revealed a role for PARP-1 in the induction of neural apoptosis in a cellular model of cerebral ischemia and suggested the possible use of PARP inhibitors as a new therapeutic intervention...
January 17, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28095320/lethal-dysregulation-of-energy-metabolism-during-embryonic-vitamin-e-deficiency
#4
Melissa McDougall, Jaewoo Choi, Hye-Kyeong Kim, Gerd Bobe, J Frederik Stevens, Enrique Cadenas, Robert Tanguay, Maret G Traber
Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality. We investigated the underlying mechanisms causing lethality using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality. VitE deficiency resulted in peroxidation of docosahexaenoic acid (DHA), depleting DHA-containing phospholipids, especially phosphatidylcholine, which also caused choline depletion. This increased lipid peroxidation also increased NADPH oxidation, which depleted glucose by shunting it to the pentose phosphate pathway...
January 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28093354/low-dose-resveratrol-ameliorates-mitochondrial-respiratory-dysfunction-and-enhances-cellular-reprogramming
#5
Yuki Mizuguchi, Hideyuki Hatakeyama, Kou Sueoka, Mamoru Tanaka, Yu-Ichi Goto
Mitochondrial disease is associated with a wide variety of clinical presentations, even among patients carrying heteroplasmic mitochondrial DNA (mtDNA) mutations, probably because of variations in mutant mtDNA proportions at the tissue and organ levels. Although several case reports and clinical trials have assessed the effectiveness of various types of drugs and supplements for the treatment of mitochondrial diseases, there are currently no cures for these conditions. In this study, we demonstrated for the first time that low dose resveratrol (RSV) ameliorated mitochondrial respiratory dysfunction in patient-derived fibroblasts carrying homoplasmic mtDNA mutations...
January 13, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28090081/metabolic-reprogramming-and-tolerance-during-sepsis-induced-aki
#6
REVIEW
Hernando Gómez, John A Kellum, Claudio Ronco
The host defence against infection is an adaptive response in which several mechanisms are deployed to decrease the pathogen load, limit tissue injury and restore homeostasis. In the past few years new evidence has suggested that the ability of the immune system to limit the microbial burden - termed resistance - might not be the only defence mechanism. In fact, the capacity of the host to decrease its own susceptibility to inflammation- induced tissue damage - termed tolerance - might be as important as resistance in determining the outcome of the infection...
January 16, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28079253/epithelial-mesenchymal-transition-emt-a-biological-process-in-the-development-stem-cell-differentiation-and-tumorigenesis
#7
REVIEW
Tong Chen, Yanan You, Hua Jiang, Zack Z Wang
The lineage transition between epithelium and mesenchyme is a process known as epithelial-mesenchymal transition (EMT), by which polarized epithelial cells lose their adhesion property and obtain mesenchymal cell phenotypes. EMT is a biological process that is often involved in embryogenesis and diseases, such as cancer invasion and metastasis. The EMT and the reverse process, mesenchymal-epithelial transition (MET), also play important roles in stem cell differentiation and de-differentiation (or reprogramming)...
January 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28075486/highly-expandable-human-ips-cell-derived-neural-progenitor-cells-npc-and-neurons-for-central-nervous-system-disease-modeling-and-high-throughput-screening
#8
Chialin Cheng, Daniel M Fass, Kat Folz-Donahue, Marcy E MacDonald, Stephen J Haggarty
Reprogramming of human somatic cells into induced pluripotent stem (iPS) cells has greatly expanded the set of research tools available to investigate the molecular and cellular mechanisms underlying central nervous system (CNS) disorders. Realizing the promise of iPS cell technology for the identification of novel therapeutic targets and for high-throughput drug screening requires implementation of methods for the large-scale production of defined CNS cell types. Here we describe a protocol for generating stable, highly expandable, iPS cell-derived CNS neural progenitor cells (NPC) using multi-dimensional fluorescence activated cell sorting (FACS) to purify NPC defined by cell surface markers...
January 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28068482/metabolic-reprogramming-in-brain-tumors
#9
Sriram Venneti, Craig B Thompson
Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. We discuss how some of these genetic alterations in brain tumors rewire metabolism...
December 21, 2016: Annual Review of Pathology
https://www.readbyqxmd.com/read/28060321/imaging-of-cell-shape-alteration-and-cell-movement-in-drosophila-gastrulation-using-de-cadherin-reporter-transgenic-flies
#10
M Rezaul Karim, Tomohiro Haruta, Taro Matsumoto, Hiroki Oda, Hiroaki Taniguchi
Gastrulation is the first set of morphologically dynamic events that occur during the embryonic development of multicellular animals such as Drosophila. This morphological alteration is also recognized as epithelial to mesenchymal transition (EMT). Dysregulation of EMT is associated with fibrosis and cancer metastasis. There is emerging evidence that EMT is controlled by a number of molecular mechanisms. As such, many key genes that control apical constriction are also known to be important factors in the EMT observed in cancer metastasis...
December 29, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28059768/sox2-promotes-lineage-plasticity-and-antiandrogen-resistance-in-tp53-and-rb1-deficient-prostate-cancer
#11
Ping Mu, Zeda Zhang, Matteo Benelli, Wouter R Karthaus, Elizabeth Hoover, Chi-Chao Chen, John Wongvipat, Sheng-Yu Ku, Dong Gao, Zhen Cao, Neel Shah, Elizabeth J Adams, Wassim Abida, Philip A Watson, Davide Prandi, Chun-Hao Huang, Elisa de Stanchina, Scott W Lowe, Leigh Ellis, Himisha Beltran, Mark A Rubin, David W Goodrich, Francesca Demichelis, Charles L Sawyers
Some cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. We use in vitro and in vivo human prostate cancer models to show that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR)-dependent luminal epithelial cells to AR-independent basal-like cells. This lineage plasticity is enabled by the loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2, and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression...
January 6, 2017: Science
https://www.readbyqxmd.com/read/28057861/cellular-context-dependent-consequences-of-apc-mutations-on-gene-regulation-and-cellular-behavior
#12
Kyoichi Hashimoto, Yosuke Yamada, Katsunori Semi, Masaki Yagi, Akito Tanaka, Fumiaki Itakura, Hitomi Aoki, Takahiro Kunisada, Knut Woltjen, Hironori Haga, Yoshiharu Sakai, Takuya Yamamoto, Yasuhiro Yamada
The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an Apc(Min/+) (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression...
January 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28054643/network-based-approach-to-identify-potential-targets-and-drugs-that-promote-neuroprotection-and-neurorepair-in-acute-ischemic-stroke
#13
Yiwei Wang, Hailong Liu, Yongzhong Lin, Guangming Liu, Hongwei Chu, Pengyao Zhao, Xiaohan Yang, Tiezheng Zheng, Ming Fan, Xuezhong Zhou, Jun Meng, Changkai Sun
Acute ischemic stroke (AIS) accounts for more than 80% of the approximately 610,000 new stroke cases worldwide every year. Both ischemia and reperfusion can cause death, damage, and functional changes of affected nerve cells, and these alterations can result in high rates of disability and mortality. Therefore, therapies aimed at increasing neuroprotection and neurorepair would make significant contributions to AIS management. However, with regard to AIS therapies, there is currently a large gap between experimental achievements and practical clinical solutions (EC-GAP-AIS)...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053954/targeting-lipid-metabolic-reprogramming-as-anticancer-therapeutics
#14
REVIEW
Ji-Young Cha, Ho-Jae Lee
Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells can affect numerous cellular processes, including cell growth, proliferation, differentiation, and survival...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28053233/dual-specificity-phosphatase-5-controls-the-localized-inhibition-propagation-and-transforming-potential-of-erk-signaling
#15
Andrew M Kidger, Linda K Rushworth, Julia Stellzig, Jane Davidson, Christopher J Bryant, Cassidy Bayley, Edward Caddye, Tim Rogers, Stephen M Keyse, Christopher J Caunt
Deregulated extracellular signal-regulated kinase (ERK) signaling drives cancer growth. Normally, ERK activity is self-limiting by the rapid inactivation of upstream kinases and delayed induction of dual-specificity MAP kinase phosphatases (MKPs/DUSPs). However, interactions between these feedback mechanisms are unclear. Here we show that, although the MKP DUSP5 both inactivates and anchors ERK in the nucleus, it paradoxically increases and prolongs cytoplasmic ERK activity. The latter effect is caused, at least in part, by the relief of ERK-mediated RAF inhibition...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28052084/linking-hematopoietic-differentiation-to-co-expressed-sets-of-pluripotency-associated-and-imprinted-genes-and-to-regulatory-microrna-transcription-factor-motifs
#16
Mohamed Hamed, Johannes Trumm, Christian Spaniol, Riccha Sethi, Mohammad R Irhimeh, Georg Fuellen, Martina Paulsen, Volkhard Helms
Maintenance of cell pluripotency, differentiation, and reprogramming are regulated by complex gene regulatory networks (GRNs) including monoallelically-expressed imprinted genes. Besides transcriptional control, epigenetic modifications and microRNAs contribute to cellular differentiation. As a model system for studying the capacity of cells to preserve their pluripotency state and the onset of differentiation and subsequent specialization, murine hematopoiesis was used and compared to embryonic stem cells (ESCs) as a control...
2017: PloS One
https://www.readbyqxmd.com/read/28049629/integrated-metabolomics-and-proteomics-highlight-altered-nicotinamide-and-polyamine-pathways-in-lung-adenocarcinoma
#17
REVIEW
Johannes F Fahrmann, Dmitry D Grapov, Kwanjeera Wanichthanarak, Brian C DeFelice, Michelle R Salemi, William N Rom, David R Gandara, Brett S Phinney, Oliver Fiehn, Harvey Pass, Suzanne Miyamoto
Lung cancer is the leading cause of cancer mortality in the United States with non-small cell lung cancer (NSCLC) adenocarcinoma being the most common histological type. Early perturbations in cellular metabolism are a hallmark of cancer, but the extent of these changes in early stage lung adenocarcinoma remains largely unknown. In the current study, an integrated metabolomics and proteomics approach was utilized to characterize the biochemical and molecular alterations between malignant and matched control tissue from 27 subjects diagnosed with early stage lung adenocarcinoma...
January 3, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28049151/modulation-of-microrna-mrna-target-pairs-by-human-papillomavirus-16-oncoproteins
#18
Mallory E Harden, Nripesh Prasad, Anthony Griffiths, Karl Munger
: The E6 and E7 proteins are the major oncogenic drivers encoded by high-risk human papillomaviruses (HPVs). While many aspects of the transforming activities of these proteins have been extensively studied, there are fewer studies that have investigated how HPV E6/E7 expression affects the expression of cellular noncoding RNAs. The goal of our study was to investigate HPV16 E6/E7 modulation of cellular microRNA (miR) levels and to determine the potential consequences for cellular gene expression...
January 3, 2017: MBio
https://www.readbyqxmd.com/read/28040634/insights-on-germinability-and-desiccation-tolerance-in-developing-neem-seeds-azadirachta-indica-role-of-aos-antioxidative-enzymes-and-dehydrin-like-protein
#19
Balram Sahu, Alok Kumar Sahu, Srinivasa Rao Chennareddy, Avinash Soni, Subhash Chandra Naithani
The germinability and desiccation tolerance (DT) in developing seed are regulated by cellular metabolism involving active oxygen species (AOS) and protective proteins during maturation drying. The aim of the present investigation was to unravel the functions of AOS (superoxide, H2O2 and OH-radical), antioxidative enzymes (SOD, CAT and APX) and dehydrin-like proteins in regulating the germinability and DT in undried and artificially desiccated developing neem seeds. Germination was first observed in seeds of 8 weeks after anthesis (waa) whereas DT was noticed from 9 waa...
December 25, 2016: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28025745/microrna-98-suppress-warburg-effect-by-targeting-hk2-in-colon-cancer-cells
#20
Weimin Zhu, Yijiao Huang, Qi Pan, Pei Xiang, Nanlan Xie, Hao Yu
BACKGROUND: Warburg effect is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRs) could regulate such metabolic reprograming. Aberrant expression of miR-98 has been observed in many types of cancers. However, its functions and significance in colon cancer remain largely elusive. AIMS: To investigate miR-98 expression and the biological functions in colon cancer progression. METHODS: miR-98 expression levels were determined by quantitative RT-PCR in 215 cases of colon cancer samples...
December 26, 2016: Digestive Diseases and Sciences
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