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https://www.readbyqxmd.com/read/28231508/regulating-dynamic-signaling-between-hematopoietic-stem-cells-and-niche-cells-via-a-hydrogel-matrix
#1
Bhushan P Mahadik, Narayanan A K Bharadwaj, Randy H Ewoldt, Brendan A C Harley
Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin(+)) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin(+) cells increased myeloid differentiation...
February 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28231326/expression-of-glyoxalase-i-is-reduced-in-cirrhotic-livers-a-possible-mechanism-in-the-development-of-cirrhosis
#2
Marcus Hollenbach, Antje Thonig, Sabine Pohl, Cristina Ripoll, Maurice Michel, Alexander Zipprich
BACKGROUND: High concentrations of methylglyoxal (MGO) cause cytotoxiticy via formation of advanced glycation endproducts (AGEs) and inflammation. MGO is detoxificated enzymatically by glyoxalase-I (Glo-I). The aim of this study was to analyze the role of Glo-I during the development of cirrhosis. METHODS: In primary hepatocytes, hepatic stellate cells (pHSC) and sinusoidal endothelial cells (pLSEC) from rats with early (CCl4 8wk) and advanced cirrhosis (CCl4 12wk) expression and activity of Glo-I were determined and compared to control...
2017: PloS One
https://www.readbyqxmd.com/read/28224997/clonal-reversal-of-ageing-associated-stem-cell-lineage-bias-via-a-pluripotent-intermediate
#3
Martin Wahlestedt, Eva Erlandsson, Trine Kristiansen, Rong Lu, Cord Brakebusch, Irving L Weissman, Joan Yuan, Javier Martin-Gonzalez, David Bryder
Ageing associates with significant alterations in somatic/adult stem cells and therapies to counteract these might have profound benefits for health. In the blood, haematopoietic stem cell (HSC) ageing is linked to several functional shortcomings. However, besides the recent realization that individual HSCs might be preset differentially already from young age, HSCs might also age asynchronously. Evaluating the prospects for HSC rejuvenation therefore ultimately requires approaching those HSCs that are functionally affected by age...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28218906/differential-cytokine-contributions-of-perivascular-haematopoietic-stem-cell-niches
#4
Noboru Asada, Yuya Kunisaki, Halley Pierce, Zichen Wang, Nicolas F Fernandez, Alexander Birbrair, Avi Ma'ayan, Paul S Frenette
Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218745/human-%C3%AE-%C3%AE-t-cells-are-quickly-reconstituted-after-stem-cell-transplantation-and-show-adaptive-clonal-expansion-in-response-to-viral-infection
#5
Sarina Ravens, Christian Schultze-Florey, Solaiman Raha, Inga Sandrock, Melanie Drenker, Linda Oberdörfer, Annika Reinhardt, Inga Ravens, Maleen Beck, Robert Geffers, Constantin von Kaisenberg, Michael Heuser, Felicitas Thol, Arnold Ganser, Reinhold Förster, Christian Koenecke, Immo Prinz
To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private...
February 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28212548/branched-chain-amino-acids-prevent-hepatic-fibrosis-and-development-of-hepatocellular-carcinoma-in-a-non-alcoholic-steatohepatitis-mouse-model
#6
Kai Takegoshi, Masao Honda, Hikari Okada, Riuta Takabatake, Naoto Matsuzawa-Nagata, Jean S Campbell, Masashi Nishikawa, Tetsuro Shimakami, Takayoshi Shirasaki, Yoshio Sakai, Taro Yamashita, Toshinari Takamura, Takuji Tanaka, Shuichi Kaneko
Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28202942/duration-of-shiv-production-by-infected-cells-is-not-exponentially-distributed-implications-for-estimates-of-infection-parameters-and-antiviral-efficacy
#7
Catherine A A Beauchemin, Tomoyuki Miura, Shingo Iwami
The duration of the eclipse phase, from cell infection to the production and release of the first virion progeny, immediately followed by the virus-production phase, from the first to the last virion progeny, are important steps in a viral infection, by setting the pace of infection progression and modulating the response to antiviral therapy. Using a mathematical model (MM) and data for the infection of HSC-F cells with SHIV in vitro, we reconfirm our earlier finding that the eclipse phase duration follows a fat-tailed distribution, lasting 19 h (18-20 h)...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202494/fumarate-hydratase-is-a-critical-metabolic-regulator-of-hematopoietic-stem-cell-functions
#8
Amelie V Guitart, Theano I Panagopoulou, Arnaud Villacreces, Milica Vukovic, Catarina Sepulveda, Lewis Allen, Roderick N Carter, Louie N van de Lagemaat, Marcos Morgan, Peter Giles, Zuzanna Sas, Marta Vila Gonzalez, Hannah Lawson, Jasmin Paris, Joy Edwards-Hicks, Katrin Schaak, Chithra Subramani, Deniz Gezer, Alejandro Armesilla-Diaz, Jimi Wills, Aaron Easterbrook, David Coman, Chi Wai Eric So, Donal O'Carroll, Douglas Vernimmen, Neil P Rodrigues, Patrick J Pollard, Nicholas M Morton, Andrew Finch, Kamil R Kranc
Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure...
February 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28196601/cholinergic-signals-from-the-cns-regulate-g-csf-mediated-hsc-mobilization-from-bone-marrow-via-a-glucocorticoid-signaling-relay
#9
Halley Pierce, Dachuan Zhang, Claire Magnon, Daniel Lucas, John R Christin, Matthew Huggins, Gary J Schwartz, Paul S Frenette
Hematopoietic stem cells (HSCs) are mobilized from niches in the bone marrow (BM) to the blood circulation by the cytokine granulocyte colony-stimulating factor (G-CSF) through complex mechanisms. Among these, signals from the sympathetic nervous system regulate HSC egress via its niche, but how the brain communicates with the BM remains largely unknown. Here we show that muscarinic receptor type-1 (Chrm1) signaling in the hypothalamus promotes G-CSF-elicited HSC mobilization via hormonal priming of the hypothalamic-pituitary-adrenal (HPA) axis...
February 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28194671/activation-of-insulin-pi3k-akt-p70s6k-pathway-in-hepatic-stellate-cells-contributes-to-fibrosis-in-nonalcoholic-steatohepatitis
#10
Cindy X Cai, Hema Buddha, Shobha Castelino-Prabhu, Zhiwei Zhang, Robert S Britton, Bruce R Bacon, Brent A Neuschwander-Tetri
BACKGROUND AND AIMS: Hyperinsulinemia and insulin resistance are hallmark features of nonalcoholic fatty liver disease and steatohepatitis (NASH). It remains unclear whether and how insulin contributes to the development of fibrosis in NASH. In this study, we explored insulin signaling in the regulation of hepatic stellate cell (HSC) activation and the progression of NASH-fibrosis. METHODS: Phosphorylation of Akt and p70S6K were examined in primary HSC and in a rat model of NASH-fibrosis induced by high-fat and high-cholesterol diet for 24 weeks...
February 13, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28193525/caffeic-acid-phenethyl-ester-attenuates-liver-fibrosis-via-inhibition-of-tgf-%C3%AE-1-smad3-pathway-and-induction-of-autophagy-pathway
#11
Ning Yang, Shuangsuo Dang, Juanjuan Shi, Fengping Wu, Mei Li, Xin Zhang, Yaping Li, Xiaoli Jia, Song Zhai
Caffeic acid phenethyl ester (CAPE) has been reported to possess the hepatoprotective effect. This study was to investigate the mechanism underlying CAPE against liver fibrosis in a liver fibrosis model induced by toxic carbon tetrachloride (CCl4) in male Sprague-Dawley rats and in vitro in CAPE (5 μM, 10 μM, 15 μM) treated hepatic stellate cells (HSC-T6). We found that CAPE treatment remarkably attenuated CCl4-induced liver fibrosis by blocking the activation of HSCs as determined by the expression alternation of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), collage I, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28191767/concise-review-paracrine-functions-of-vascular-niche-cells-in-regulating-hematopoietic-stem-cell-fate
#12
Joshua P Sasine, Kelly T Yeo, John P Chute
The functions of endothelial cells (ECs) in regulating oxygen delivery, nutrient exchange, coagulation, and transit of inflammatory cells throughout the body are well--established. ECs have also been shown to regulate the maintenance and regeneration of organ-specific stem cells in mammals. In the hematopoietic system, hematopoietic stem cells (HSCs) are dependent on signals from the bone marrow (BM) vascular niche for their maintenance and regeneration after myelosuppressive injury. Recent studies have demonstrated the essential functions of BM ECs and perivascular stromal cells in regulating these processes...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188823/hepatic-stellate-cell-interferes-with-nk-cell-regulation-of-fibrogenesis-via-curcumin-induced-senescence-of-hepatic-stellate-cell
#13
Huanhuan Jin, Yan Jia, Zhen Yao, Jingjing Huang, Meng Hao, Shunyu Yao, Naqi Lian, Feng Zhang, Chenxi Zhang, Xingran Chen, Mianli Bian, Jiangjuan Shao, Li Wu, Anping Chen, Shizhong Zheng
Hepatic fibrosis, a common scarring response to various forms of chronic liver injury, is a precursor to cirrhosis and liver cancer. During liver fibrosis, hepatic stellate cells (HSCs) initially activate and proliferate, which are responsible for the secretion of extracellular matrix components. However, these cells eventually senesce and are cleared by natural killer (NK) cells. Our previous researches have shown that the natural product curcumin could promote the senescence of activated HSC. In this study, we investigated how NK cells target senescent HSC and assessed the effect of this process on liver fibrosis...
February 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28187462/recombinant-tat-bmi-1-fusion-protein-induces-ex-vivo-expansion-of-human-umbilical-cord-blood-derived-hematopoietic-stem-cells
#14
Bruna Codispoti, Nicola Rinaldo, Emanuela Chiarella, Michela Lupia, Cristina Barbara Spoleti, Maria Grazia Marafioti, Annamaria Aloisio, Stefania Scicchitano, Marco Giordano, Giovanna Nappo, Valeria Lucchino, Malcolm A S Moore, Pengbo Zhou, Maria Mesuraca, Heather Mandy Bond, Giovanni Morrone
Transplantation of hematopoietic stem cells (HSCs) is a well-established therapeutic approach for numerous disorders. HSCs are typically derived from bone marrow or peripheral blood after cytokine-induced mobilization. Umbilical cord blood (CB) represents an appealing alternative HSC source, but the small amounts of the individual CB units have limited its applications. The availability of strategies for safe ex vivo expansion of CB-derived HSCs (CB-HSCs) may allow to extend the use of these cells in adult patients and to avoid the risk of insufficient engraftment or delayed hematopoietic recovery...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186156/mechanism-study-on-the-sulfidation-of-zno-with-sulfur-and-iron-oxide-at-high-temperature
#15
Junwei Han, Wei Liu, Tianfu Zhang, Kai Xue, Wenhua Li, Fen Jiao, Wenqing Qin
The mechanism of ZnO sulfidation with sulfur and iron oxide at high temperatures was studied. The thermodynamic analysis, sulfidation behavior of zinc, phase transformations, morphology changes, and surface properties were investigated by HSC 5.0 combined with FactSage 7.0, ICP, XRD, optical microscopy coupled with SEM-EDS, and XPS. The results indicate that increasing temperature and adding iron oxide can not only improve the sulfidation of ZnO but also promote the formation and growth of ZnS crystals. Fe2O3 captured the sulfur in the initial sulfidation process as iron sulfides, which then acted as the sulfurizing agent in the late period, thus reducing sulfur escape at high temperatures...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28184331/verticillin-a-inhibits-leiomyosarcoma-and-malignant-peripheral-nerve-sheath-tumor-growth-via-induction-of-apoptosis
#16
A Zewdu, G Lopez, D Braggio, C Kenny, D Constantino, H K Bid, K Batte, O H Iwenofu, N H Oberlies, C J Pearce, A M Strohecker, D Lev, R E Pollock
OBJECTIVE: The heterogeneity of soft tissue sarcoma (STS) represents a major challenge for the development of effective therapeutics. Comprised of over 50 different histology subtypes of various etiologies, STS subsets are further characterized as either karyotypically simple or complex. Due to the number of genetic anomalies associated with genetically complex STS, development of therapies demonstrating potency against this STS cluster is especially challenging and yet greatly needed...
November 2016: Clinical & Experimental Pharmacology
https://www.readbyqxmd.com/read/28182733/pyruvate-dehydrogenase-kinase-1-is-essential-for-transplantable-mouse-bone-marrow-hematopoietic-stem-cell-and-progenitor-function
#17
Camilla Halvarsson, Pernilla Eliasson, Jan-Ingvar Jönsson
BACKGROUND: Accumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1α (HIF-1α) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types...
2017: PloS One
https://www.readbyqxmd.com/read/28179281/scl-tal1-a-multi-faceted-regulator-from-blood-development-to-disease
#18
Catherine Porcher, Hedia Chagraoui, Maiken S Kristiansen
SCL/TAL1 is an essential transcription factor in normal and malignant hematopoiesis. It is required for specification of the blood program during development, adult hematopoietic stem cell (HSC) survival and quiescence, and terminal maturation of select blood lineages. Following ectopic expression, SCL contributes to oncogenesis in T-cell acute lymphoblastic leukemia (T-ALL). Remarkably, SCL's activities are all mediated through nucleation of a core quaternary protein complex (SCL:E-protein:LMO2:LDB1) and dynamic recruitment of conserved combinatorial associations of additional regulators in a lineage- and stage-specific context...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28179275/granulocyte-colony-stimulating-factor-mobilizes-dormant-hematopoietic-stem-cells-without-proliferation-in-mice
#19
Jeffrey M Bernitz, Michael Daniel, Yesai S Fstkchyan, Kateri Moore
Granulocyte colony stimulating factor (G-CSF) is used clinically to treat leukopenia and to enforce hematopoietic stem cell (HSC) mobilization to the peripheral blood (PB). However, G-CSF is also produced in response to infection, and excessive exposure reduces HSC repopulation capacity. Previous work has shown that dormant HSCs contain all the long-term repopulation potential in the bone marrow (BM), and that as HSCs accumulate a divisional history they progressively lose regenerative potential. As G-CSF treatment also induces HSC proliferation, we sought to examine whether G-CSF-mediated repopulation defects are due to increased proliferative history...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28177770/interleukin-6-secreted-by-bipotential-murine-oval-liver-stem-cells-induces-apoptosis-of-activated-hepatic-stellate-cells-by-activating-nf-%C3%AE%C2%BAb-inducible-nitric-oxide-synthase-signaling
#20
Palanivel Gajalakshmi, Syamantak Majumder, Cornelia S Viebahn, Akila Swaminathan, George Yeoh, Suvro Dr Chatterjee
Liver fibrosis is now well recognized as the causative factor for the increased mortality from complications associated with liver pathologies. Activated hepatic stellate cells (HSCs) play a critical role in the progression of liver fibrosis. Therefore, targeting these activated HSCs to prevent and/or treat liver disease is a worthwhile approach to explore. In the present in vitro study, we investigated the use of bipotential murine oval liver cells (BMOL) in regulating the functions of activated hepatic stellate cells (HSCs) to prevent progression of liver fibrosis...
October 9, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
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