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Stem cell metabolism

Daniel Wai-Hung Ho, Regina Cheuk-Lam Lo, Lo-Kong Chan, Irene Oi-Lin Ng
The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. The next-generation sequencing technology is facilitating the global and systematic evaluation of molecular landscapes in HCC. There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development. Moreover, recent studies have identified distinct surface markers of cancer stem cell (CSC) in HCC, and they also put forward the profound involvement of altered signaling pathways and epigenetic modifications in CSCs, in addition to the concomitant drug resistance and metastasis...
October 2016: Liver Cancer
Jakub Smolar, Souzan Salemi, Maya Horst, Tullio Sulser, Daniel Eberli
Conditions impairing bladder function in children and adults, such as myelomeningocele, posterior urethral valves, bladder exstrophy or spinal cord injury, often need urinary diversion or augmentation cystoplasty as when untreated they may cause severe bladder dysfunction and kidney failure. Currently, the gold standard therapy of end-stage bladder disease refractory to conservative management is enterocystoplasty, a surgical enlargement of the bladder with intestinal tissue. Despite providing functional improvement, enterocystoplasty is associated with significant long-term complications, such as recurrent urinary tract infections, metabolic abnormalities, stone formation, and malignancies...
September 2016: Transfusion Medicine and Hemotherapy
Liangliang Quan, Yang Wang, Jiulong Liang, Tao Qiu, Hongyi Wang, Ye Zhang, Yu Zhang, Qiang Hui, Kai Tao
In the present study, we aimed to reveal the molecular mechanisms responsible for the differentiation of human adipose tissue-derived stem cells (hASCs) into myocytes and osteoblasts. Microarray data GSE37329 were obtained from the Gene Expression Omnibus database, including three hASC cell lines from healthy donors, two osteogenic lineages and two myogenic lineages from the in vitro‑induction of hASCs. Differentially expressed genes (DEGs) in the two lineages were firstly screened. Subsequently, the underlying functions of the two sets of DEGs were investigated by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, followed by protein-protein interaction (PPI) network construction...
October 25, 2016: International Journal of Molecular Medicine
Pavel Sumazin, Yidong Chen, Lisa R Treviño, Stephen F Sarabia, Oliver A Hampton, Kayuri Patel, Toni-Ann Mistretta, Barry Zorman, Patrick Thompson, Andras Heczey, Sarah Comerford, David A Wheeler, Murali Chintagumpala, Rebecka Meyers, Dinesh Rakheja, Milton J Finegold, Gail Tomlinson, D Williams Parsons, Dolores López-Terrada
Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pre-treatment tumors have been molecularly profiled and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pre-treatment HBs at diagnosis. Our analysis of 88 clinically-annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated NFE2L2 activity, high LIN28B, HMGA2, SALL4 and AFP expression, and high coordinated expression of oncofetal proteins and stem cell markers; while low-risk tumors had low LIN28B and let-7 expression, and high HNF1A activity...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hayoung Jang, Minsung Kim, Soyoung Lee, Jungtae Kim, Dong-Cheol Woo, Kyung Won Kim, Kyuyoung Song, Inchul Lee
Adipose tissue hyperplasia with increased number of adipocytes is implicated in a protective rather than deleterious effect on obesity-associated metabolic disorder. It is poorly understood how the adipose tissue cellularity is regulated. Tc1 is a gene of vertebrates that regulates diverse downstream genes. Young Tc1-deleted mice fed on standard chow diet show expanded adipose tissue with smaller adipocytes in size compared to wild type controls, representing adipose tissue hyperplasia. Tc1(-/-) mice show enhanced glucose tolerance and reduced serum lipids...
October 24, 2016: Scientific Reports
Shizhong Ke, Shuzhen Chen, Zihui Dong, Christopher S Hong, Qi Zhang, Liang Tang, Pinghua Yang, Jian Zhai, Hexin Yan, Feng Shen, Zhengping Zhuang, Wen Wen, Hongyang Wang
: Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma (HCC). Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. Here we demonstrated an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas (TCGA). In the subset of HCC patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting impairment of respiratory metabolism, which sequentially led to depletion of α-ketoglutarate, stabilization of hypoxia inducible factor-α and expression of target genes such as EPO...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Fernando J Martinez, Gabriel A Pratt, Eric L Van Nostrand, Ranjan Batra, Stephanie C Huelga, Katannya Kapeli, Peter Freese, Seung J Chun, Karen Ling, Chelsea Gelboin-Burkhart, Layla Fijany, Harrison C Wang, Julia K Nussbacher, Sara M Broski, Hong Joo Kim, Rea Lardelli, Balaji Sundararaman, John P Donohue, Ashkan Javaherian, Jens Lykke-Andersen, Steven Finkbeiner, Frank Bennett, Manuel Ares, Christopher B Burge, J Paul Taylor, Frank Rigo, Gene W Yeo
HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. HnRNP A2/B1 loss results in alternative splicing (AS), including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism...
October 13, 2016: Neuron
Clive J Curley, Eimear B Dolan, Brenton Cavanagh, Janice O'Sullivan, Garry P Duffy, Bruce P Murphy
Localized delivery of stem cells is potentially a promising therapeutic strategy for regenerating damaged myocardium. Many studies focus on limiting the biologic component of cell loss, but few address the contribution of mechanical factors. This study investigates optimal parameters for retaining the largest volume of cell loaded hydrogels post intramyocardial injection, without compromising cell viability. In vitro, hydrogel was injected into porcine hearts using various needle designs. Hydrogel retention and distribution pattern was then determined...
October 20, 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Carmela Nardelli, Ilaria Granata, Laura Iaffaldano, Valeria D'Argenio, Valentina Del Monaco, Giuseppe Maria Maruotti, Daniela Omodei, Luigi Del Vecchio, Pasquale Martinelli, Francesco Salvatore, Mario Rosario Guarracino, Lucia Sacchetti, Lucio Pastore
Clinical findings and data obtained in animal models indicate that nutrient uptake and exposure to environmental agents during pregnancy may affect fetal/newborn gestational programming thereby resulting in obesity and/or obesity-related disorders in offspring. Human amniotic mesenchymal stem cells (hA-MSCs) differentiate into adipocytes, and are thus a suitable model to investigate adipocyte functions in obesity. The aim of this study was to elucidate the miRNome of hA-MSCs and its contribution to obesity in pregnancy...
October 20, 2016: Stem Cells and Development
Amanda Faria Assoni, Giuliana Castello, Marcos Valadares, Melinda Beccari, Juliana Gomes, Mayra Pelatti, Miguel Mitne-Neto, Valdemir Melechco Carvalho, Mayana Zatz
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by null mutations in the dystrophin gene. Although the primary defect is the deficiency of muscle dystrophin, secondary events, including chronic inflammation, fibrosis and muscle regeneration failure are thought to actively contribute to disease progression. Despite several advances, there is still no effective therapy for DMD. Therefore, the potential regenerative capacities, as well as immune-privileged properties of Mesenchymal Stromal Cells (MSCs), have been the focus of intense investigation in different animal models aiming the treatment of these disorders...
October 20, 2016: Stem Cells and Development
Himalee S Sabnis, Heath L Bradley, Shweta Tripathi, Wen-Mei Yu, William Tse, Cheng-Kui Qu, Kevin D Bunting
Current therapy for acute myeloid leukemia (AML) primarily includes high-dose cytotoxic chemotherapy with or without allogeneic stem cell transplantation. Targeting unique cellular metabolism of cancer cells is a potentially less toxic approach. Monotherapy with mitochondrial inhibitors like metformin have met with limited success since escape mechanisms such as increased glycolytic ATP production, especially in hyperglycemia, can overcome the metabolic blockade. As an alternative strategy for metformin therapy, we hypothesized that the combination of 6-benzylthioinosine (6-BT), a broad-spectrum metabolic inhibitor, and metformin could block this drug resistance mechanism...
October 5, 2016: Leukemia Research
Guang Yang, Gonzalo I Cancino, Siraj K Zahr, Axel Guskjolen, Anastassia Voronova, Denis Gallagher, Paul W Frankland, David R Kaplan, Freda D Miller
Maternal diabetes is known to adversely influence brain development in offspring. Here, we provide evidence that this involves the circulating metabolite methylglyoxal, which is increased in diabetes, and its detoxifying enzyme, glyoxalase 1 (Glo1), which when mutated is associated with neurodevelopmental disorders. Specifically, when Glo1 levels were decreased in embryonic mouse cortical neural precursor cells (NPCs), this led to premature neurogenesis and NPC depletion embryonically and long-term alterations in cortical neurons postnatally...
October 18, 2016: Cell Reports
Theerawut Chanmee, Pawared Ontong, Tomomi Izumikawa, Miho Higashide, Nobutoshi Mochizuki, Chatchadawalai Chokchaitaweesuk, Manatsanan Khansai, Kazuki Nakajima, Ikuko Kakizaki, Prachya Kongtawelert, Naoyuki Taniguchi, Naoki Itano
Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. Like many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known on how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem-cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells...
October 6, 2016: Journal of Biological Chemistry
Sarah Tessier, Natalia Martin-Martin, Hugues de Thé, Arkaitz Carracedo, Valerie Lallemand-Breitenbach
SIGNIFICANCE: Cellular metabolic activity impacts on the production of reactive oxygen species (ROS), both positively through mitochondrial oxidative processes and negatively by promoting the production of reducing agents (including NADPH and reduced glutathione). A defined metabolic state in cancer cells is critical for cell growth and long-term self-renewal, and such state is intrinsically associated to redox balance. Promyelocytic leukemia protein (PML) regulates several biological processes, at least in part through its ability to control the assembly of PML Nuclear Bodies (PML NBs)...
October 19, 2016: Antioxidants & Redox Signaling
Sofia A V Fortunato, Michel Vervoort, Marcin Adamski, Maja Adamska
BACKGROUND: Basic Helix-Loop-Helix (bHLH) genes encode a large family of eukaryotic transcription factors, categorized into six high-order groups: pan-eukaryotic group B involved in regulation of cell cycle, metabolism, and development; holozoan-specific groups C and F involved in development and maintenance of homeostasis; and metazoan-specific groups A, D and E including well-studied genes, such as Atonal, Twist and Hairy, with diverse developmental roles including control of morphogenesis and specification of neurons...
2016: EvoDevo
Claudia Compagnucci, Emanuela Piermarini, Antonella Sferra, Rossella Borghi, Alessia Niceforo, Stefania Petrini, Fiorella Piemonte, Enrico Bertini
Patient-derived induced pluripotent stem cells (iPSCs) provide a novel tool to investigate the pathophysiology of poorly known diseases, in particular those affecting the nervous system, which has been difficult to study for its lack of accessibility. In this emerging and promising field, recent iPSCs studies are mostly used as "proof-of-principle" experiments that are confirmatory of previous findings obtained from animal models and postmortem human studies; its promise as a discovery tool is just beginning to be realized...
October 15, 2016: Molecular and Cellular Neurosciences
Mohammad Massumi, Farzaneh Pourasgari, Amarnadh Nalla, Battsetseg Batchuluun, Kristina Nagy, Eric Neely, Rida Gull, Andras Nagy, Michael B Wheeler
The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems...
2016: PloS One
Martino Deidda, Rosalinda Madonna, Ruggiero Mango, Pasquale Pagliaro, Pier P Bassareo, Lucia Cugusi, Silvio Romano, Maria Penco, Francesco Romeo, Giuseppe Mercuro
Despite advances in supportive and protective therapy for myocardial function, heart failure caused by various clinical conditions, including cardiomyopathy due to antineoplastic therapy, remains a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators have been searching for alternative treatments that can effectively repair the damaged heart and permanently restore its function. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as trastuzumab...
May 2016: Journal of Cardiovascular Medicine
Stacey S Huppert, Kathleen M Campbell
PURPOSE OF REVIEW: Although the liver possesses a unique, innate ability to regenerate through mass compensation, transplantation remains the only therapy when damage outpaces regeneration, or liver metabolic capacity is irreversibly impacted. Recent insight from developmental biology has greatly influenced the advancement of alternative options to transplantation in these settings. RECENT FINDINGS: Factors known to direct liver cell specification, expansion, and differentiation have been used to generate hepatocyte-like cells from stem and somatic cells for developing cell therapies...
October 15, 2016: Current Opinion in Organ Transplantation
Sung-Eun Lim, Virginie Esain, Wanda Kwan, Lindsay N Theodore, Mauricio Cortes, Isaura M Frost, Sarah Y Liu, Trista E North
Hematopoietic stem cells (HSCs) have the ability to both self-renew and differentiate into all the mature blood cell lineages and thereby reconstitute the entire blood system. As such, HSCs are therapeutically valuable for treatment of hematological malignances and bone marrow failure. We recently showed that transient glucose elevation elicited dose-dependent effects on HSCs through elevated metabolic activity and subsequent ROS-mediated induction of Hypoxia Inducible Factor 1α (Hif1α). Platelet Derived Growth Factor B (pdgfb), a Hif1α-target, and its receptor, pdgfrb, were significantly upregulated in response to metabolic stimulation...
October 14, 2016: Experimental Hematology
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