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https://www.readbyqxmd.com/read/29126263/notch-signaling-regulates-differentiation-and-steroidogenesis-in-female-mouse-ovarian-granulosa-cells
#1
Rexxi D Prasasya, Kelly E Mayo
The Notch pathway is a highly conserved juxtacrine signaling mechanism that is important for many cellular processes during development, including differentiation and proliferation. While Notch is important during ovarian follicle formation and early development, its functions during the gonadotropin-dependent stages of follicle development are largely unexplored. We observed positive regulation of Notch activity and expression of Notch ligands and receptors following activation of the LH-receptor in prepubertal mouse ovary...
November 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/29057904/the-ank-repeats-of-notch-4-int3-activate-nf-%C3%AE%C2%BAb-canonical-pathway-in-the-absence-of-rbpj-and-causes-mammary-tumorigenesis
#2
Ahmed Raafat, Sharon Bargo, David McCurdy, Robert Callahan
Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in the mammary gland have two phenotypes exhibited with 100% penetrance: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch-4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. Interestingly, WAP-Int3/Rbpj knockout mice have normal mammary gland development but still developed mammary tumors with a slightly longer latency than the WAP-Int3 mice...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038527/blood-vessel-control-of-macrophage-maturation-promotes-arteriogenesis-in-ischemia
#3
Kashyap Krishnasamy, Anne Limbourg, Tamar Kapanadze, Jaba Gamrekelashvili, Christian Beger, Christine Häger, Vladimir J Lozanovski, Christine S Falk, L Christian Napp, Johann Bauersachs, Matthias Mack, Hermann Haller, Christian Weber, Ralf H Adams, Florian P Limbourg
Ischemia causes an inflammatory response that is intended to restore perfusion and homeostasis yet often aggravates damage. Here we show, using conditional genetic deletion strategies together with adoptive cell transfer experiments in a mouse model of hind limb ischemia, that blood vessels control macrophage differentiation and maturation from recruited monocytes via Notch signaling, which in turn promotes arteriogenesis and tissue repair. Macrophage maturation is controlled by Notch ligand Dll1 expressed in vascular endothelial cells of arteries and requires macrophage canonical Notch signaling via Rbpj, which simultaneously suppresses an inflammatory macrophage fate...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29030483/rbpj-cbf1-interacts-with-l3mbtl3-mbt1-to-promote-repression-of-notch-signaling-via-histone-demethylase-kdm1a-lsd1
#4
Tao Xu, Sung-Soo Park, Benedetto Daniele Giaimo, Daniel Hall, Francesca Ferrante, Diana M Ho, Kazuya Hori, Lucas Anhezini, Iris Ertl, Marek Bartkuhn, Honglai Zhang, Eléna Milon, Kimberly Ha, Kevin P Conlon, Rork Kuick, Brandon Govindarajoo, Yang Zhang, Yuqing Sun, Yali Dou, Venkatesha Basrur, Kojo Sj Elenitoba-Johnson, Alexey I Nesvizhskii, Julian Ceron, Cheng-Yu Lee, Tilman Borggrefe, Rhett A Kovall, Jean-François Rual
Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor...
November 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29023469/the-common-oncogenomic-program-of-notch1-and-notch3-signaling-in-t-cell-acute-lymphoblastic-leukemia
#5
Sung Hee Choi, Eric Severson, Warren S Pear, Xiaole S Liu, Jon C Aster, Stephen C Blacklow
Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL), in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells...
2017: PloS One
https://www.readbyqxmd.com/read/28923841/a-novel-notch-yap-circuit-drives-stemness-and-tumorigenesis-in-embryonal-rhabdomyosarcoma
#6
Katherine K Slemmons, Lisa E S Crose, Stefan Riedel, Manuela Sushnitha, Brian Belyea, Corinne M Linardic
Rhabdomyosarcoma (RMS), a cancer characterized by skeletal muscle features, is the most common soft-tissue sarcoma of childhood. While low- and intermediate-risk groups have seen improved outcomes, high-risk patients still face a 5-year survival rate of <30%, a statistic that has not changed in over 40 years. Understanding the biologic underpinnings of RMS is critical. The developmental pathways of Notch and YAP have been identified as potent but independent oncogenic signals that support the embryonal variant of RMS (eRMS)...
September 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28877478/the-ulk3-kinase-is-critical-for-convergent-control-of-cancer-associated-fibroblast-activation-by-csl-and-gli
#7
Sandro Goruppi, Maria-Giuseppina Procopio, Seunghee Jo, Andrea Clocchiatti, Victor Neel, G Paolo Dotto
The connection between signaling pathways activating cancer-associated fibroblasts (CAFs) remains to be determined. Metabolic alterations linked to autophagy have also been implicated in CAF activation. CSL/RBPJ, a transcriptional repressor that mediates Notch signaling, suppresses the gene expression program(s), leading to stromal senescence and CAF activation. Deregulated GLI signaling can also contribute to CAF conversion. Here, we report that compromised CSL function depends on GLI activation for conversion of human dermal fibroblasts into CAFs, separately from cellular senescence...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28771710/brain-endothelial-cells-induce-astrocytic-expression-of-the-glutamate-transporter-glt-1-by-a-notch-dependent-mechanism
#8
Meredith L Lee, Zila Martinez-Lozada, Elizabeth N Krizman, Michael B Robinson
Neuron-secreted factors induce astrocytic expression of the glutamate transporter, GLT-1 (excitatory amino acid transporter 2). In addition to their elaborate anatomic relationships with neurons, astrocytes also have processes that extend to and envelop the vasculature. Although previous studies have demonstrated that brain endothelia contribute to astrocyte differentiation and maturation, the effects of brain endothelia on astrocytic expression of GLT-1 have not been examined. In this study, we tested the hypothesis that endothelia induce expression of GLT-1 by co-culturing astrocytes from mice that utilize non-coding elements of the GLT-1 gene to control expression of reporter proteins with the mouse endothelial cell line, bEND...
December 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28729299/notch2-blockade-enhances-hematopoietic-stem-cell-mobilization-and-homing
#9
Weihuan Wang, Shuiliang Yu, Jay Myers, Yiwei Wang, William W Xin, Marwah Albakri, Alison W Xin, Ming Li, Alex Y Huang, Wei Xin, Christian W Siebel, Hillard M Lazarus, Lan Zhou
Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation (HCT) may only mobilize limited numbers of hematopoietic progenitor cells (HPCs) into blood, precluding use of the procedure, or being placed at increased risk of complications due to slow hematopoietic reconstitution. Developing more efficacious HPC mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is not essential for homeostasis of adult hematopoietic stem cells (HSCs), Notch-ligand adhesive interaction maintains HSC quiescence and niche retention...
October 2017: Haematologica
https://www.readbyqxmd.com/read/28580186/mash1-dependent-notch-signaling-pathway-regulates-gabaergic-neuron-like-differentiation-from-bone-marrow-derived-mesenchymal-stem-cells
#10
Qianfa Long, Qiang Luo, Kai Wang, Adrian Bates, Ashok K Shetty
GABAergic neuronal cell grafting has promise for treating a multitude of neurological disorders including epilepsy, age-related memory dysfunction, Alzheimer's disease and schizophrenia. However, identification of an unlimited source of GABAergic cells is critical for advancing such therapies. Our previous study implied that reprogramming of bone marrow-derived mesenchymal stem cells (BMSCs) through overexpression of the Achaete-scute homolog 1 (Ascl1, also called Mash1) could generate GABAergic neuron-like cells...
May 2017: Aging and Disease
https://www.readbyqxmd.com/read/28573150/notch-hes-signaling-and-mir-9-engage-in-complex-feedback-interactions-controlling-neural-progenitor-cell-proliferation-and-differentiation
#11
REVIEW
Beate Roese-Koerner, Laura Stappert, Oliver Brüstle
Canonical Notch signaling has diverse functions during nervous system development and is critical for neural progenitor self-renewal, timing of differentiation and specification of various cell fates. A key feature of Notch-mediated self-renewal is its fluctuating activity within the neural progenitor cell population and the oscillatory expression pattern of the Notch effector Hes1 and its target genes. A negative feedback loop between Hes1 and neurogenic microRNA miR-9 was found to be part of this oscillatory clock...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28571041/cbf1-is-clinically-prognostic-and-serves-as-a-target-to-block-cellular-invasion-and-chemoresistance-of-emt-like-glioblastoma-cells
#12
D Maciaczyk, D Picard, L Zhao, K Koch, D Herrera-Rios, G Li, V Marquardt, D Pauck, T Hoerbelt, W Zhang, D M Ouwens, M Remke, T Jiang, H J Steiger, J Maciaczyk, U D Kahlert
BACKGROUND: Glioblastoma is the most common and most lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) is the cardinal transcriptional regulator of the Notch signalling network and has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some of the malignant properties of CSCs are mediated through the activation of pro-invasive programme of epithelial-to-mesenchymal transition (EMT)...
June 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28487372/structure-function-analysis-of-rbp-j-interacting-and-tubulin-associated-rita-reveals-regions-critical-for-repression-of-notch-target-genes
#13
Nassif Tabaja, Zhenyu Yuan, Franz Oswald, Rhett A Kovall
The Notch pathway is a cell-to-cell signaling mechanism that is essential for tissue development and maintenance, and aberrant Notch signaling has been implicated in various cancers, congenital defects, and cardiovascular diseases. Notch signaling activates the expression of target genes, which are regulated by the transcription factor CSL (CBF1/RBP-J, Su(H), Lag-1). CSL interacts with both transcriptional corepressor and coactivator proteins, functioning as both a repressor and activator, respectively. Although Notch activation complexes are relatively well understood at the structural level, less is known about how CSL interacts with corepressors...
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28465505/hypertension-reduces-soluble-guanylyl-cyclase-expression-in-the-mouse-aorta-via-the-notch-signaling-pathway
#14
Catarina Rippe, Baoyi Zhu, Katarzyna K Krawczyk, Ed Van Bavel, Sebastian Albinsson, Jonas Sjölund, Erik N T P Bakker, Karl Swärd
Hypertension is a dominating risk factor for cardiovascular disease. To characterize the genomic response to hypertension, we administered vehicle or angiotensin II to mice and performed gene expression analyses. AngII treatment resulted in a robust increase in blood pressure and altered expression of 235 genes in the aorta, including Gucy1a3 and Gucy1b3 which encode subunits of soluble guanylyl cyclase (sGC). Western blotting and immunohistochemistry confirmed repression of sGC associated with curtailed relaxation via sGC activation...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28455378/g9a-controls-placental-vascular-maturation-by-activating-the-notch-pathway
#15
Lijun Chi, Abdalla Ahmed, Anna R Roy, Sandra Vuong, Lindsay S Cahill, Laura Caporiccio, John G Sled, Isabella Caniggia, Michael D Wilson, Paul Delgado-Olguin
Defective fetoplacental vascular maturation causes intrauterine growth restriction (IUGR). A transcriptional switch initiates placental maturation, during which blood vessels elongate. However, the cellular mechanisms and regulatory pathways involved are unknown. We show that the histone methyltransferase G9a, also known as Ehmt2, activates the Notch pathway to promote placental vascular maturation. Placental vasculature from embryos with G9a-deficient endothelial progenitor cells failed to expand owing to decreased endothelial cell proliferation and increased trophoblast proliferation...
June 1, 2017: Development
https://www.readbyqxmd.com/read/28401892/notch-and-hippo-signaling-converge-on-strawberry-notch-1-sbno1-to-synergistically-activate-cdx2-during-specification-of-the-trophectoderm
#16
Yusuke Watanabe, Kota Y Miyasaka, Atsushi Kubo, Yasuyuki S Kida, Osamu Nakagawa, Yoshikazu Hirate, Hiroshi Sasaki, Toshihiko Ogura
The first binary cell fate decision occurs at the morula stage and gives rise to two distinct types of cells that constitute the trophectoderm (TE) and inner cell mass (ICM). The cell fate determinant, Cdx2, is induced in TE cells and plays an essential role in their differentiation and maintenance. Notch and Hippo signaling cascades are assumed to converge onto regulatory elements of Cdx2, however, the underlying molecular mechanisms are largely unknown. Here, we show involvement of Strawberry Notch1 (Sbno1), a novel chromatin factor of the helicase superfamily 2, during preimplantation development...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28377481/characterization-of-an-immunogenic-mutation-in-a-patient-with-metastatic-triple-negative-breast-cancer
#17
Yasmine Assadipour, Nikolaos Zacharakis, Jessica S Crystal, Todd D Prickett, Jared J Gartner, Robert P T Somerville, Hui Xu, Mary A Black, Li Jia, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John R Wunderlich, Zhili Zheng, Yong-Chen Lu, Paul F Robbins, Steven A Rosenberg, Stephanie L Goff, Steven A Feldman
Purpose: The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There are limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic nonsynonymous mutations in a patient with triple-negative breast cancer (TNBC) to identify and isolate mutation-reactive TILs for possible use in adoptive cell transfer...
April 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28362378/combining-intravital-fluorescent-microscopy-ivfm-with-genetic-models-to-study-engraftment-dynamics-of-hematopoietic-cells-to-bone-marrow-niches
#18
Lin Wang, Malgorzata M Kamocka, Amy Zollman, Nadia Carlesso
Increasing evidence indicates that normal hematopoiesis is regulated by distinct microenvironmental cues in the BM, which include specialized cellular niches modulating critical hematopoietic stem cell (HSC) functions(1)(,)(2). Indeed, a more detailed picture of the hematopoietic microenvironment is now emerging, in which the endosteal and the endothelial niches form functional units for the regulation of normal HSC and their progeny(3)(,)(4)(,)(5). New studies have revealed the importance of perivascular cells, adipocytes and neuronal cells in maintaining and regulating HSC function(6)(,)(7)(,)(8)...
March 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28215940/elf5-is-a-principal-cell-lineage-specific-transcription-factor-in-the-kidney-that-contributes-to-aqp2-and-avpr2-gene-expression
#19
Justin Grassmeyer, Malini Mukherjee, Jennifer deRiso, Casey Hettinger, Monica Bailey, Satrajit Sinha, Jane E Visvader, Haotian Zhao, Eric Fogarty, Kameswaran Surendran
The mammalian kidney collecting ducts are critical for water, electrolyte and acid-base homeostasis and develop as a branched network of tubular structures composed of principal cells intermingled with intercalated cells. The intermingled nature of the different collecting duct cell types has made it challenging to identify unique and critical factors that mark and/or regulate the development of the different collecting duct cell lineages. Here we report that the canonical Notch signaling pathway components, RBPJ and Presinilin1 and 2, are involved in patterning the mouse collecting duct cell fates by maintaining a balance between principal cell and intercalated cell fates...
April 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28163017/small-molecule-inhibitors-of-the-sox18-transcription-factor
#20
Frank Fontaine, Jeroen Overman, Mehdi Moustaqil, Sreeman Mamidyala, Angela Salim, Kamesh Narasimhan, Nina Prokoph, Avril A B Robertson, Linda Lua, Kirill Alexandrov, Peter Koopman, Robert J Capon, Emma Sierecki, Yann Gambin, Ralf Jauch, Matthew A Cooper, Johannes Zuegg, Mathias Francois
Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors...
March 16, 2017: Cell Chemical Biology
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