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https://www.readbyqxmd.com/read/28729299/notch2-blockade-enhances-hematopoietic-stem-cell-mobilization-and-homing
#1
Weihuan Wang, Shuiliang Yu, Jay Myers, Yiwei Wang, William W Xin, Marwah Alkabri, 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 may mobilize limited numbers of hematopoietic progenitor cells into blood, precluding use of the procedure, or being placed at increased risk for complications due to slow hematopoietic reconstitution. Developing more efficacious hematopoietic progenitor cell mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is dispensable for homeostasis of adult hematopoietic stem cells, Notch-ligand adhesive interaction maintains hematopoietic stem cell quiescence and niche retention...
July 20, 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
#2
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
#3
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
#4
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
#5
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
#6
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/ehmt2-g9a-controls-placental-vascular-maturation-by-activating-the-notch-pathway
#7
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 where blood vessels elongate. However, cellular mechanisms and regulatory pathways involved are unknown. We show that the histone methyltransferase Ehmt2, also known as G9a, activates the Notch pathway to promote placental vascular maturation. Placental vasculature from embryos with G9a-deficient endothelial progenitor cells failed to expand due to decreased endothelial cell proliferation and increased trophoblast proliferation...
April 28, 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
#8
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
#9
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
The administration of autologous tumor infiltrating lymphocytes (TIL) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There is limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic non-synonymous mutations in a patient with triple-negative breast cancer (TNBC) in order to identify and isolate mutation-reactive TIL 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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28160419/adams-oliver-syndrome-review-of-the-literature-refining-the-diagnostic-phenotype
#13
REVIEW
Susan Hassed, Shibo Li, John Mulvihill, Christopher Aston, Susan Palmer
The Adams-Oliver syndrome (AOS) is defined as aplasia cutis congenita (ACC) with transverse terminal limb defects (TTLD). Frequencies of associated anomalies are not well characterized. Six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. We review 385 previously described individuals (139 non-familial and 246 familial probands and family members) and add clinical data on 13 previously unreported individuals with AOS. In addition to ACC and TTLD, the most commonly associated anomalies included a wide variety of central nervous system (CNS) anomalies and congenital heart defects each seen in 23%...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28030855/a-rare-de-novo-interstitial-duplication-at-4p15-2-in-a-boy-with-severe-congenital-heart-defects-limb-anomalies-hypogonadism-and-global-developmental-delay
#14
Liyang Liang, Yingjun Xie, Yiping Shen, Qibin Yin, Haiming Yuan
Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments...
2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28027012/dynamic-chromatin-regulation-at-notch-target-genes
#15
Benedetto Daniele Giaimo, Franz Oswald, Tilman Borggrefe
RBPJ is the central transcription factor that controls the Notch-dependent transcriptional response by coordinating repressing histone H3K27 deacetylation and activating histone H3K4 methylation. Here, we discuss the molecular mechanisms how RBPJ interacts with opposing NCoR/HDAC-corepressing or KMT2D/UTX-coactivating complexes and how this is controlled by phosphorylation of chromatin modifiers.
January 2017: Transcription
https://www.readbyqxmd.com/read/28009085/protein-tyrosine-phosphatase-prl2-mediates-notch-and-kit-signals-in-early-t-cell-progenitors
#16
Michihiro Kobayashi, Sarah C Nabinger, Yunpeng Bai, Momoko Yoshimoto, Rui Gao, Sisi Chen, Chonghua Yao, Yuanshu Dong, Lujuan Zhang, Sonia Rodriguez, Yumi Yashiro-Ohtani, Warren S Pear, Nadia Carlesso, Mervin C Yoder, Reuben Kapur, Mark H Kaplan, Hugo Daniel Lacorazza, Zhong-Yin Zhang, Yan Liu
The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors...
April 2017: Stem Cells
https://www.readbyqxmd.com/read/27939883/indispensable-role-of-notch-ligand-dependent-signaling-in-the-proliferation-and-stem-cell-niche-maintenance-of-apc-deficient-intestinal-tumors
#17
Toru Nakata, Hiromichi Shimizu, Sayaka Nagata, Go Ito, Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Fumiaki Ishibashi, Reiko Kuno, Sho Anzai, Tatsuro Murano, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Katsuto Hozumi, Mamoru Watanabe, Ryuichi Okamoto
Ligand-dependent activation of Notch signaling is required to maintain the stem-cell niche of normal intestinal epithelium. However, the precise role of Notch signaling in the maintenance of the intestinal tumor stem cell niche and the importance of the RBPJ-independent non-canonical pathway in intestinal tumors remains unknown. Here we show that Notch signaling was activated in LGR5(+ve) cells of APC-deficient mice intestinal tumors. Accordingly, Notch ligands, including Jag1, Dll1, and Dll4, were expressed in these tumors...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27936142/gene-co-expression-network-analysis-unraveling-transcriptional-regulation-of-high-altitude-adaptation-of-tibetan-pig
#18
Cunling Jia, Xiaoyan Kong, James E Koltes, Xiao Gou, Shuli Yang, Dawei Yan, Shaoxiong Lu, Zehui Wei
Tibetan pigs have survived at high altitude for millennia and they have a suite of adaptive features to tolerate the hypoxic environment. However, the molecular mechanisms underlying the regulation of hypoxia-adaptive phenotypes have not been completely elucidated. In this study, we analyzed differentially expressed genes (DEGs), biological pathways and constructed co-expression regulation networks using whole-transcriptome microarrays from lung tissues of Tibetan and Duroc pigs both at high and low altitude...
2016: PloS One
https://www.readbyqxmd.com/read/27904763/microrna-133a-3p-exerts-inhibitory-effects-on-gallbladder-carcinoma-via-targeting-rbpj
#19
Yuan Huang, Yaoshi Wu, Jiahong Dong, Dongdong Han, Shiwei Yang, Lin Jiang
Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with high mortality. The median survival time is 6 months, and the 5-year survival rate less than 5% for GBC patients. Thus, it is imperative to investigate the molecular mechanisms underlying the pathogenesis of GBC. miR-133a may exert anti-tumor effects on a variety of cancers. However, the role of miR-133a in the pathogenesis of GBC remains unclear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) showed the miR-133a-3p expression markedly decreased in GBC as compared to adjacent normal tissues...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27791012/notch3-drives-development-and-progression-of-cholangiocarcinoma
#20
Rachel V Guest, Luke Boulter, Benjamin J Dwyer, Timothy J Kendall, Tak-Yung Man, Sarah E Minnis-Lyons, Wei-Yu Lu, Andrew J Robson, Sofia Ferreira Gonzalez, Alexander Raven, Davina Wojtacha, Jennifer P Morton, Mina Komuta, Tania Roskams, Stephen J Wigmore, Owen J Sansom, Stuart J Forbes
The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
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