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https://www.readbyqxmd.com/read/28654695/fate-of-tenogenic-differentiation-potential-of-human-bone-marrow-stromal-cells-by-uniaxial-stretching-affected-by-stretch-activated-calcium-channel-agonist-gadolinium
#1
Hui Yin Nam, Hanumantha Rao Balaji Raghavendran, Belinda Pingguan-Murphy, Azlina A Abbas, Azhar M Merican, Tunku Kamarul
The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated...
2017: PloS One
https://www.readbyqxmd.com/read/28654420/lineage-commitment-of-embryonic-cells-involves-mek1-dependent-clearance-of-pluripotency-regulator-ventx2
#2
Pierluigi Scerbo, Leslie Marchal, Laurent Kodjabachian
During early embryogenesis, cells must exit pluripotency and commit to multiple lineages in all germ-layers. How this transition is operated in vivo is poorly understood. Here, we report that MEK1 and the Nanog-related transcription factor Ventx2 coordinate this transition. MEK1 was required to make Xenopus pluripotent cells competent to respond to all cell fate inducers tested. Importantly, MEK1 activity was necessary to clear the pluripotency protein Ventx2 at the onset of gastrulation. Thus, concomitant MEK1 and Ventx2 knockdown restored the competence of embryonic cells to differentiate...
June 27, 2017: ELife
https://www.readbyqxmd.com/read/28654046/hypoxic-preconditioning-of-marrow-derived-progenitor-cells-as-a-source-for-the-generation-of-mature-schwann-cells
#3
Yat-Ping Tsui, Alan Kwan-Long Mung, Ying-Shing Chan, Daisy Kwok-Yan Shum, Graham Ka-Hon Shea
This manuscript describes a means to enrich for neural progenitors from the marrow stromal cell (MSC) population and thereafter to direct them to the mature Schwann cell fate. We subjected rat and human MSCs to transient hypoxic conditions (1% oxygen for 16 h) followed by expansion as neurospheres upon low-attachment substratum with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) supplementation. Neurospheres were seeded onto poly-D-lysine/laminin-coated tissue culture plastic and cultured in a gliogenic cocktail containing β-Heregulin, bFGF, and platelet-derived growth factor (PDGF) to generate Schwann cell-like cells (SCLCs)...
June 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28652378/caenorhabditis-elegans-ces-1-snail-represses-pig-1-melk-expression-to-control-asymmetric-cell-division
#4
Hai Wei, Bo Yan, Julien Gagneur, Barbara Conradt
Snail-like transcription factors affect stem cell function through mechanisms that are incompletely understood. In the C. elegans NSM neuroblast lineage, CES-1 Snail coordinates cell cycle progression and cell polarity to ensure the asymmetric division of the NSM neuroblast and the generation of two daughter cells of different sizes and fates. We have previously shown that CES-1 Snail controls cell cycle progression by repressing the expression of cdc-25.2 CDC25. However, the mechanism through which CES-1 Snail affects cell polarity has been elusive...
June 26, 2017: Genetics
https://www.readbyqxmd.com/read/28652368/antagonistic-bmp-cwnt-signaling-in-the-cnidarian-nematostella-vectensis-reveals-insight-into-the-evolution-of-mesoderm
#5
Naveen Wijesena, David K Simmons, Mark Q Martindale
Gastrulation was arguably the key evolutionary innovation that enabled metazoan diversification, leading to the formation of distinct germ layers and specialized tissues. Differential gene expression specifying cell fate is governed by the inputs of intracellular and/or extracellular signals. Beta-catenin/Tcf and the TGF-beta bone morphogenetic protein (BMP) provide critical molecular signaling inputs during germ layer specification in bilaterian metazoans, but there has been no direct experimental evidence for a specific role for BMP signaling during endomesoderm specification in the early branching metazoan Nematostella vectensis (an anthozoan cnidarian)...
June 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28652317/the-protein-phosphatase-4-complex-promotes-the-notch-pathway-and-wingless-transcription
#6
Eric T Hall, Tirthadipa Pradhan-Sundd, Faaria Samnani, Esther M Verheyen
The Wnt/Wingless (Wg) pathway controls cell fate specification, tissue differentiation and organ development across organisms. Using an in vivo RNAi screen to identify novel kinase and phosphatase regulators of the Wg pathway, we identified subunits of the serine threonine phosphatase Protein phosphatase 4 (PP4). Knockdown of the catalytic and the regulatory subunits of PP4 cause reductions in the Wg pathway targets Senseless and Distal-less. We find that PP4 regulates the Wg pathway by controlling Notch-driven wg transcription...
June 26, 2017: Biology Open
https://www.readbyqxmd.com/read/28652304/thymic-progenitors-of-tcr%C3%AE-%C3%AE-cd8%C3%AE-%C3%AE-intestinal-intraepithelial-lymphocytes-require-rasgrp1-for-development
#7
Dominic P Golec, Romy E Hoeppli, Laura M Henao Caviedes, Jillian McCann, Megan K Levings, Troy A Baldwin
Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRαβ(+)CD8αα intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling...
June 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28652219/the-fate-of-the-brain-cholinergic-neurons-in-neurodegenerative-diseases
#8
REVIEW
Giancarlo Pepeu, Maria Grazia Giovannini
The aims of this review are: 1) to describe which cholinergic neurons are affected in brain neurodegenerative diseases leading to dementia; 2) to discuss the possible causes of the degeneration of the cholinergic neurons, 3) to summarize the functional consequences of the cholinergic deficit. The brain cholinergic system is basically constituted by three populations of phenotypically similar neurons forming a series of basal forebrain nuclei, the midpontine nuclei and a large population of striatal interneurons...
June 23, 2017: Brain Research
https://www.readbyqxmd.com/read/28651594/the-cd4-t-cell-regulatory-network-mediates-inflammatory-responses-during-acute-hyperinsulinemia-a-simulation-study
#9
Mariana E Martinez-Sanchez, Marcia Hiriart, Elena R Alvarez-Buylla
BACKGROUND: Obesity is frequently linked to insulin resistance, high insulin levels, chronic inflammation, and alterations in the behaviour of CD4+ T cells. Despite the biomedical importance of this condition, the system-level mechanisms that alter CD4+ T cell differentiation and plasticity are not well understood. RESULTS: We model how hyperinsulinemia alters the dynamics of the CD4+ T regulatory network, and this, in turn, modulates cell differentiation and plasticity...
June 26, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28650568/enhanced-functional-properties-of-human-limbal-stem-cells-by-inhibition-of-the-mir-31-fih-1-p21-axis
#10
Zhiping Liu, Weijiao Zhan, Minzhi Zeng, Jinghong Chen, Huyong Zou, Zhiqun Min
OBJECTIVE: On the basis of the functional roles of the embryonic stem cell niche (ESCN) in the human limbal stem cells (LSCs), we proposed to explore the potential roles of microRNAs in regulating the self-renewal and differentiation of LSCs cultured in the ESCN. METHODS: The LSCs were cultured in different media, either in CnT-20 media or in CnT-20 + 20% ES culture supernatant (ESC-CM). The LSCs cultured in ESC-CM were then transfected with microRNA-31 (miR-31) mimic or antago-31...
June 26, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28650529/metal-ions-activated-dnazymes-used-for-regulation-of-telomerase-activity-in-living-cells
#11
Xiaogang Qu, Jiasi Wang, Hongshuang Qin, Faming Wang, Jinsong Ren
Telomerase is a key regulator in cell metabolism, tissue renewal and organismal lifespan. Here we develop a simple strategy to modulate cellular telomerase activity, and further control cell fate based on Mg2+ and Zn2+ activated DNAzymes in living cells. Through modulation of telomerase activity, we can regulate cell behavior, including cell migration, cell differentiation, cell senescence and cell cycle. Our work provides a new way to modulate telomerase activity in living cells by using DNAzymes.
June 26, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#12
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650342/inflammatory-ly6chi-monocytes-and-their-conversion-to-m2-macrophages-drive-atherosclerosis-regression
#13
Karishma Rahman, Yuliya Vengrenyuk, Stephen A Ramsey, Noemi Rotllan Vila, Natasha M Girgis, Jianhua Liu, Viktoria Gusarova, Jesper Gromada, Ada Weinstock, Kathryn J Moore, P'ng Loke, Edward A Fisher
Atherosclerosis is a chronic inflammatory disease, and developing therapies to promote its regression is an important clinical goal. We previously established that atherosclerosis regression is characterized by an overall decrease in plaque macrophages and enrichment in markers of alternatively activated M2 macrophages. We have now investigated the origin and functional requirement for M2 macrophages in regression in normolipidemic mice that received transplants of atherosclerotic aortic segments. We compared plaque regression in WT normolipidemic recipients and those deficient in chemokine receptors necessary to recruit inflammatory Ly6Chi (Ccr2-/- or Cx3cr1-/-) or patrolling Ly6Clo (Ccr5-/-) monocytes...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28649977/convection-shapes-the-trade-off-between-antibiotic-efficacy-and-the-selection-for-resistance-in-spatial-gradients
#14
Matti Gralka, Diana Fusco, Stephen Martis, Oskar Hallatschek
Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A key question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance...
June 26, 2017: Physical Biology
https://www.readbyqxmd.com/read/28649443/a-multiscale-model-of-early-cell-lineage-specification-including-cell-division
#15
Alen Tosenberger, Didier Gonze, Sylvain Bessonnard, Michel Cohen-Tannoudji, Claire Chazaud, Geneviève Dupont
Embryonic development is a self-organised process during which cells divide, interact, change fate according to a complex gene regulatory network and organise themselves in a three-dimensional space. Here, we model this complex dynamic phenomenon in the context of the acquisition of epiblast and primitive endoderm identities within the inner cell mass of the preimplantation embryo in the mouse. The multiscale model describes cell division and interactions between cells, as well as biochemical reactions inside each individual cell and in the extracellular matrix...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28648899/transient-hes5-activity-instructs-mesodermal-cells-toward-a-cardiac-fate
#16
Ana G Freire, Avinash Waghray, Francisca Soares-da-Silva, Tatiana P Resende, Dung-Fang Lee, Carlos-Filipe Pereira, Diana S Nascimento, Ihor R Lemischka, Perpétua Pinto-do-Ó
Notch signaling plays a role in specifying a cardiac fate but the downstream effectors remain unknown. In this study we implicate the Notch downstream effector HES5 in cardiogenesis. We show transient Hes5 expression in early mesoderm of gastrulating embryos and demonstrate, by loss and gain-of-function experiments in mouse embryonic stem cells, that HES5 favors cardiac over primitive erythroid fate. Hes5 overexpression promotes upregulation of the cardiac gene Isl1, while the hematopoietic regulator Scl is downregulated...
June 21, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28648843/identification-of-regulators-of-germ-stem-cell-enwrapment-by-its-niche-in-c-elegans
#17
Lara M Linden, Kacy L Gordon, Ariel M Pani, Sara G Payne, Aastha Garde, Dane Burkholder, Qiuyi Chi, Bob Goldstein, David R Sherwood
Many stem cell niches contain support cells that increase contact with stem cells by enwrapping them in cellular processes. One example is the germ stem cell niche in C. elegans, which is composed of a single niche cell termed the distal tip cell (DTC) that extends cellular processes, constructing an elaborate plexus that enwraps germ stem cells. To identify genes required for plexus formation and to explore the function of this specialized enwrapping behavior, a series of targeted and tissue-specific RNAi screens were performed...
June 22, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28648560/switch-like-behavior-enables-wnt11-concentration-specific-response-during-dorso-ventral-axis-formation-in-xenopus-laevis
#18
Jan Eric Sträng, Rainer Schuler, Michael Kühl, Hans A Kestler
Wnt signaling plays a role in diverse processes such as cell proliferation, differentiation, migration or cell polarity. Dysfunction of Wnt signaling is associated with human diseases and aging. Wnts can activate several interacting intracellular signaling pathways, in particular the so called canonical and non-canonical pathways. The canonical Wnt response leads to a stabilization of cytoplasmic β-catenin whereas non-canonical Wnt signaling can result in the activation of calcium-calmodulin dependent kinase II (CamKII)...
June 23, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28647433/targeted-release-of-transcription-factors-for-human-cell-reprogramming-by-zebra-cell-penetrating-peptide
#19
Benjamin Caulier, Lionel Berthoin, Helène Coradin, Frédéric Garban, Marie Claire Dagher, Benoît Polack, Bertrand Toussaint, Jean Luc Lenormand, David Laurin
Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements...
June 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28647367/mitochondrial-quality-control-pathways-pink1-acts-as-a-gatekeeper
#20
Elvira P Leites, Vanessa A Morais
Mitochondria have a pivotal role in the maintenance of cell homeostasis and survival. Mitochondria are involved in processes such as ATP production, reactive oxygen species production, apoptosis induction, calcium homeostasis and protein degradation. Thus, mechanisms that regulate the intrinsic quality of mitochondria have a crucial role in dictating overall cell fate. The importance of these well-regulated mechanisms is highlighted in disease scenarios such as neurodegeneration, cancer and neuromuscular atrophy...
June 21, 2017: Biochemical and Biophysical Research Communications
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