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https://www.readbyqxmd.com/read/29333477/notch-ligand-binding-assay-using-flow-cytometry
#1
Shweta Varshney, Pamela Stanley
Notch signaling is an evolutionary conserved signaling pathway that plays an indispensable role during development, and in the maintenance of homeostatic processes, in a wide variety of tissues (Kopan, 2012; Hori et al., 2013). The multifaceted roles of Notch signaling are stringently regulated at different levels. One of the most important aspects of regulation is the binding of different Notch ligands to each Notch receptor (NOTCH1-NOTCH4). Canonical ligands Delta or Serrate (in Drosophila), and Delta-like (DLL1 and DLL4) or Jagged (JAG1 and JAG2) (in mammals), are transmembrane glycoproteins...
December 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29330161/production-of-bmp4-by-endothelial-cells-is-crucial-for-endogenous-thymic-regeneration
#2
Tobias Wertheimer, Enrico Velardi, Jennifer Tsai, Kirsten Cooper, Shiyun Xiao, Christopher C Kloss, Katja J Ottmüller, Zeinab Mokhtari, Christian Brede, Paul deRoos, Sinéad Kinsella, Brisa Palikuqi, Michael Ginsberg, Lauren F Young, Fabiana Kreines, Sophia R Lieberman, Amina Lazrak, Peipei Guo, Florent Malard, Odette M Smith, Yusuke Shono, Robert R Jenq, Alan M Hanash, Daniel J Nolan, Jason M Butler, Andreas Beilhack, Nancy R Manley, Shahin Rafii, Jarrod A Dudakov, Marcel R M van den Brink
The thymus is not only extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood, and this capacity diminishes considerably with age. We show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signaling or production by either pharmacologic or genetic inhibition impaired thymic repair...
January 12, 2018: Science Immunology
https://www.readbyqxmd.com/read/29329032/targeting-expression-of-adenosine-receptors-during-hypoxia-induced-angiogenesis-a-study-using-zebrafish-model
#3
Navina Panneerselvan, Malathi Ragunathan
Hypoxia is known to be a major player during pathological angiogenesis and adenosine as a negative feedback signaling to maintain oxygen delivery in pathological ischemic condition. We mimicked hypoxic condition and studied angiogenesis by inducing adenosine receptors using forskolin, a plant compound and NECA analogue of adenosine using zebrafish model. Vascular endothelial growth factor (VEGF) is known to play a key role during pathological angiogenesis and regulated by the factors HIF1a under hypoxic condition and recently Notch is proposed to play a negative feedback loop mechanism along with VEGF signaling but the role of adenosine receptor during the process is not known...
January 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29321062/notch-signaling-triggered-via-the-ligand-dll4-impedes-m2-macrophage-differentiation-and-promotes-their-apoptosis
#4
Sylvain Pagie, Nathalie Gérard, Béatrice Charreau
BACKGROUND: Notch signaling controls many cellular processes, including cell fate determination, cell differentiation, proliferation and apoptosis. In mammals, four Notch receptors (Notch 1-4) can interact with five distinct ligands [Jagged1, Jagged2, Delta-like 1 (DLL1), DLL3, and DLL4]. We previously reported that Notch activation is modulated in endothelial cells and monocytes during inflammation and showed that inflammation upregulates DLL4 on endothelial cells. DLL4 promotes differentiation of blood monocytes into proinflammatory M1 macrophages...
January 10, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29320922/co-emergence-of-specialized-endothelial-cells-from-embryonic-stem-cells
#5
Nicole Madfis, Zhiqiang Lin, Ashwath Kumar, Simone A Douglas, Manu O Platt, Yuhong Fan, Kara E McCloskey
A well-formed and robust vasculature is critical to the health of most organ systems in the body. However, the endothelial cells (ECs) forming the vasculature can exhibit a number of distinct functional subphenotypes like arterial or venous ECs, as well as angiogenic tip and stalk ECs. Here, we investigate the in vitro differentiation of EC subphenotypes from embryonic stem cells (ESCs) using. Using our staged induction methods and chemically-defined mediums, highly angiogenic EC subpopulations, as well as, less proliferative and less migratory EC subpopulations are derived...
January 10, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29246751/generation-and-characterization-of-an-anti-delta-like-ligand-4-nanobody-to-induce-non-productive-angiogenesis
#6
Rasoul Baharlou, Nader Tajik, Mahdi Behdani, Mohammad Ali Shokrgozar, Amir Hassan Zarnani, Fatemeh Shahhosseini, Mahdi Habibi-Anbouhi
Antibody-based targeting of angiogenesis is a key approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in tumor neovascular development and angiogenesis during tumor progression. It forecasts the prognosis of human malignancies and blocking its signaling can help to inhibit neovascularization and tumor metastasis. Nanobodies are the smallest antigen-binding domains of heavy chain antibodies in camelidae. The aim of this study was to develop a Nanobody against DLL4 and apply binding and functional approaches to target it...
December 12, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29246573/establishment-of-2-control-and-2-hpsc-cell-lines-constitutively-expressing-the-notch-ligand-dll4
#7
Federico González-Pozas, Rosa Montes, Joan Domingo-Reinés, Verónica Ayllón, Verónica Ramos-Mejía
The Notch ligand DLL4 has key roles during embryonic development of different tissues, but most of the data comes from animal models. Here we describe the generation and characterization of 2 human Pluripotent Stem Cell (hPSC) lines that overexpress DLL4, as well as the two corresponding control hPSC lines. DLL4 expression can be detected at the mRNA and protein level, and does not affect the pluripotency of the cells. These hPSC lines can be used to study the role of DLL4 during human embryonic development...
December 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29238518/mir-124-promotes-proliferation-and-differentiation-of-neuronal-stem-cells-through-inactivating-notch-pathway
#8
Shujie Jiao, Yaling Liu, Yaobing Yao, Junfang Teng
Background: Neural stem cells (NSCs) are able to differentiate into neurons and astroglia. miRNAs have been demonstrated to be involved in NSC self-renewal, proliferation and differentiation. However, the exact role of miR-124 in the development of NSCs and its underlying mechanism remain to be explored. Methods: Primary NSCs were isolated from embryos of Wistar rats. Immunocytochemistry was used to stain purified NSCs. miR-124, Delta-like 4 (DLL4), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), HES1, HEY2, and cyclin D1 (CCND1) expressions were detected by qRT-PCR and western blot...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29230914/delta-like-4-activates-notch3-to-regulate-self-renewal-in-skeletal-muscle-stem-cells
#9
SiewHui Low, Josephine L Barnes, Peter S Zammit, Jonathan R Beauchamp
Notch signalling is essential to maintain skeletal muscle stem cells in quiescence. The precise roles of the different Notch receptors are, however, incompletely defined. Here we demonstrate a role for Notch3 in the self-renewal of muscle stem cells. We found that Notch3 is active in quiescent C2C12 reserve cells, and Notch3 over-expression and knockdown studies in C2C12 and primary satellite cells reveal a role in self-renewal. The Notch ligand Delta-like 4 (Dll4) is expressed by newly formed myotubes and interaction with this ligand is sufficient to maintain Notch3 activity in quiescent C2C12 reserve cells to prevent activation and progression into the cell cycle...
December 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/29212792/differential-effects-of-alcohol-and-its-metabolite-acetaldehyde-on-vascular-smooth-muscle-cell-notch-signaling-and-growth
#10
Ekaterina Hatch, David Morrow, Weimin Liu, Paul A Cahill, Eileen M Redmond
Alcohol (EtOH) consumption can variously affect cardiovascular disease (CVD). Our aim was to compare the effects of EtOH and its primary metabolite acetaldehyde (ACT) on vascular smooth muscle Notch signaling and cell growth that are important for atherogenesis. Human coronary artery smooth muscle cells (HCASMC) were treated with EtOH (25 mM) or ACT (10 μM, 25 μM). As previously reported, EtOH inhibited Notch signaling and growth of HCASMC. In contrast, ACT treatment stimulated HCASMC proliferation (cell counts) and increased proliferating cell nuclear antigen (PCNA) expression, concomitant with stimulation of Notch signaling as determined by increased Notch receptor (N1, N3) and target gene (HRT 1-3) mRNA levels...
December 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29196606/control-of-endothelial-cell-tube-formation-by-notch-ligand-intracellular-domain-interactions-with-activator-protein-1-ap-1
#11
Zary Forghany, Francesca Robertson, Alicia Lundby, Jesper V Olsen, David A Baker
Notch signaling is a ubiquitous signal transduction pathway found in most if not all metazoan cell types characterized to date. It is indispensable for cell differentiation as well as tissue growth, tissue remodelling and apoptosis. Although the canonical Notch signaling pathway is well characterized, accumulating evidence points to the existence of multiple, less well-defined, layers of regulation. In this study, we investigated the function of the intracellular domain (ICD) of the Notch ligand Delta-like 4 (DLL4)...
December 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29188408/phase-ib-trial-of-the-anti-cancer-stem-cell-dll4-binding-agent-demcizumab-with-pemetrexed-and-carboplatin-as-first-line-treatment-of-metastatic-non-squamous-nsclc
#12
Mark J McKeage, Dusan Kotasek, Ben Markman, Manuel Hidalgo, Michael J Millward, Michael B Jameson, Dean L Harris, Robert J Stagg, Ann M Kapoun, Lu Xu, Brett G M Hughes
BACKGROUND: Delta-like ligand 4-Notch (DLL4-Notch) signaling contributes to the maintenance of chemotherapy-resistant cancer stem cells and tumor vasculature. OBJECTIVE: This phase IB trial of demcizumab, an IgG2 humanized monoclonal antibody directed against DLL4, was undertaken to determine its maximum tolerated dose, safety, immunogenicity, preliminary efficacy, pharmacokinetics, and pharmacodynamics, combined with standard chemotherapy. PATIENTS AND METHODS: Forty-six treatment-naive patients with metastatic non-squamous non-small cell lung cancer (NSCLC) were enrolled in this open-label, dose-escalation study using a standard 6 + 6 design...
November 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29176671/inhibition-of-delta-induced-notch-signaling-using-fucose-analogs
#13
Michael Schneider, Vivek Kumar, Lars Ulrik Nordstrøm, Lei Feng, Hideyuki Takeuchi, Huilin Hao, Vincent C Luca, K Christopher Garcia, Pamela Stanley, Peng Wu, Robert S Haltiwanger
Notch is a cell-surface receptor that controls cell-fate decisions and is regulated by O-glycans attached to epidermal growth factor-like (EGF) repeats in its extracellular domain. Protein O-fucosyltransferase 1 (Pofut1) modifies EGF repeats with O-fucose and is essential for Notch signaling. Constitutive activation of Notch signaling has been associated with a variety of human malignancies. Therefore, tools that inhibit Notch activity are being developed as cancer therapeutics. To this end, we screened L-fucose analogs for their effects on Notch signaling...
November 27, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29160307/a-non-canonical-notch-complex-regulates-adherens-junctions-and-vascular-barrier-function
#14
William J Polacheck, Matthew L Kutys, Jinling Yang, Jeroen Eyckmans, Yinyu Wu, Hema Vasavada, Karen K Hirschi, Christopher S Chen
The vascular barrier that separates blood from tissues is actively regulated by the endothelium and is essential for transport, inflammation, and haemostasis1. Haemodynamic shear stress plays a critical role in maintaining endothelial barrier function2, but how this occurs remains unknown. Here, using an engineered organotypic model of perfused microvessels and confirming in mouse models, we identify that activation of the Notch1 transmembrane receptor directly regulates vascular barrier function through a non-canonical, transcription independent signalling mechanism that drives adherens junction assembly...
November 13, 2017: Nature
https://www.readbyqxmd.com/read/29139170/single-cell-resolution-of-human-hemato-endothelial-cells-defines-transcriptional-signatures-of-hemogenic-endothelium
#15
Mathew G Angelos, Juan E Abrahante, Robert H Blum, Dan S Kaufman
Endothelial-to-hematopoietic transition (EHT) is an important stage in definitive hematopoietic development. However, the genetic mechanisms underlying human EHT remains poorly characterized. We performed single cell RNA-seq using 55 hemogenic endothelial cells (HE: CD31(+) CD144(+) CD41(-) CD43(-) CD45(-) CD73(-) RUNX1c(+) ), 47 vascular endothelial cells without hematopoietic potential (non-HE: CD31(+) CD144(+) CD41(-) CD43(-) CD45(-) CD73(-) RUNX1c(-) ), and 35 hematopoietic progenitor cells (HP: CD34(+) CD43(+) RUNX1c(+) ) derived from human embryonic stem cells (hESCs)...
November 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/29103459/protective-effect-of-shouwu-yizhi-decoction-against-vascular-dementia-by-promoting-angiogenesis
#16
Xiao-Ni Yang, Chang-Sheng Li, Chao Chen, Xiao-Yong Tang, Guang-Qing Cheng, Xia Li
Shouwu is a traditional Chinese medicine (TCM) with neuroprotective effect. Shouwu Yizhi decoction (SYD) was designed based on TCM theory. However, little is known about the roles of SYD in Vascular dementia (VaD). The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion (I/R) rat model to induce VaD. SYD administration (54 mg·kg-1) for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion (MCAO) rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test...
October 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29096712/crosstalk-between-h9n2-avian-influenza-virus-and-crypt-derived-intestinal-organoids
#17
Lulu Huang, Qihang Hou, Lulu Ye, Qian Yang, Qinghua Yu
The spread of Avian influenza virus via animal feces makes the virus difficult to prevent, which causes great threat to human health. Therefore, it is imperative to understand the survival and invasion mechanism of H9N2 virus in the intestinal mucosa. In this study, we used mouse threedimensional intestinal organoids that contained intestinal crypts and villi differentiated from intestinal stem cells to explore interactions between H9N2 avian influenza virus and the intestinal mucosa. The HA, NA, NP and PB1 genes of H9N2 viruses could be detected in intestinal organoids at 1 h, and reached peak levels at 48 h post-infection...
November 2, 2017: Veterinary Research
https://www.readbyqxmd.com/read/29068587/the-notch-signaling-pathway-in-head-and-neck-squamous-cell-carcinoma-a-meta-analysis
#18
REVIEW
Yu-Yue Zhao, Guang-Tao Yu, Ting Xiao, Jian Hu
BACKGROUND: The Notch signaling pathway has been associated with the regulation of self-renewal capacity, cell cycle exit, and survival. However, the relationship between the Notch signaling pathway and HNSCC remains controversial. OBJECTIVES: A meta-analysis was conducted to evaluate the role of Notch signaling pathway in HNSCC. MATERIAL AND METHODS: Relevant studies published until March 31, 2015 were identified by searching the PubMed, EMBASE and Ovid database...
August 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29054964/gene-expression-profiling-of-the-notch-ahr-il22-axis-at-homeostasis-and-in-response-to-tissue-injury
#19
Marc Weidenbusch, Severin Rodler, Shangqing Song, Simone Romoli, Julian A Marschner, Franziska Kraft, Alexander Holderied, Santosh Kumar, Shrikant R Mulay, Mohsen Honarpisheh, Satish Kumar Devarapu, Maciej Lech, Hans-Joachim Anders
Notch and Interleukin-22 signaling are known to regulate tissue homeostasis and response to injury in humans and mice, and the induction of endogenous arylhydrocarbon receptor ligands through Notch links the two pathways in a hierarchical fashion. However, in adults the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TACE, PSEN1, BSG/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in 10 mature murine and human organs...
October 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#20
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
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