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https://www.readbyqxmd.com/read/28935977/zebrafish-in-vivo-screening-for-compounds-amplifying-hematopoietic-stem-and-progenitor-cells-preclinical-validation-in-human-cd34-stem-and-progenitor-cells
#1
Guruchandar Arulmozhivarman, Martin Kräter, Manja Wobus, Jens Friedrichs, Elham Pishali Bejestani, Katrin Müller, Katrin Lambert, Dimitra Alexopoulou, Andreas Dahl, Martin Stöter, Marc Bickle, Nona Shayegi, Jochen Hampe, Friedrich Stölzel, Michael Brand, Malte von Bonin, Martin Bornhäuser
The identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28903040/mir-150-regulates-memory-cd8%C3%A2-t-cell-differentiation-via-c-myb
#2
Zeyu Chen, Erietta Stelekati, Makoto Kurachi, Sixiang Yu, Zhangying Cai, Sasikanth Manne, Omar Khan, Xiaolu Yang, E John Wherry
MicroRNAs play an important role in T cell responses. However, how microRNAs regulate CD8 T cell memory remains poorly defined. Here, we found that miR-150 negatively regulates CD8 T cell memory in vivo. Genetic deletion of miR-150 disrupted the balance between memory precursor and terminal effector CD8 T cells following acute viral infection. Moreover, miR-150-deficient memory CD8 T cells were more protective upon rechallenge. A key circuit whereby miR-150 repressed memory CD8 T cell development through the transcription factor c-Myb was identified...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28877957/identification-of-a-new-adtrp1-tfpi-regulatory-axis-for-the-specification-of-primitive-myelopoiesis-and-definitive-hematopoiesis
#3
Li Wang, Xiaojing Wang, Longfei Wang, Muhammad Yousaf, Jia Li, Mengxia Zuo, Zhongcheng Yang, Dongzhi Gou, Binghao Bao, Lei Li, Ning Xiang, Haibo Jia, Chengqi Xu, Qiuyun Chen, Qing Kenneth Wang
A genomic variant in the human ADTRP [androgen-dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vasculogenesis. In zebrafish, there are 2 paralogues for adtrp (i.e., adtrp1 and adtrp2)...
September 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28811300/epigenetic-regulation-by-the-menin-pathway
#4
REVIEW
Zijie Feng, Jian Ma, Xianxin Hua
There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by interacting with multiple partners to regulate cellular homeostasis of various endocrine organs. Menin has multiple functions including regulation of several important signaling pathways by controlling gene transcription...
October 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28797734/microrna-150-controls-differentiation-of-intraepithelial-lymphocytes-via-tgf-%C3%AE-receptor-ii-regulation
#5
Sang-Hwan Seo, Min Seong Jang, Doo-Jin Kim, Seok-Min Kim, Se-Chan Oh, Cho-Rok Jung, Yunji Park, Sang-Jun Ha, Haiyoung Jung, Young-Jun Park, Suk Ran Yoon, Inpyo Choi, Tae-Don Kim
BACKGROUND: Intraepithelial lymphocytes (IELs) in the intestines play pivotal roles in maintaining the integrity of the mucosa, regulating the immune cells, and protecting against pathogenic invasion. Although several extrinsic factors such as transforming growth factor-β (TGF-β) have been identified to contribute to IEL generation, intrinsic regulatory factors have not been fully determined. OBJECTIVE: Here, we investigated the regulation of IEL differentiation and the underlying mechanisms in mice...
August 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28754957/ddr2-controls-the-epithelial-mesenchymal-transition-related-gene-expression-via-c-myb-acetylation-upon-matrix-stiffening
#6
Daehwan Kim, Eunae You, Jangho Jeong, Panseon Ko, Jung-Woong Kim, Sangmyung Rhee
Increasing matrix stiffness caused by the extracellular matrix (ECM) deposition surrounding cancer cells is accompanied by epithelial-mesenchymal transition (EMT). Here, we show that expression levels of EMT marker genes along with discoidin domain receptor 2 (DDR2) can increase upon matrix stiffening. DDR2 silencing by short hairpin RNA downregulated EMT markers. Promoter analysis and chromatin immunoprecipitation revealed that c-Myb and LEF1 may be responsible for DDR2 induction during cell culture on a stiff matrix...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724215/melatonin-inhibits-proliferation-and-invasion-via-repression-of-mirna-155-in-glioma-cells
#7
Junyi Gu, Zhongsheng Lu, Chenghong Ji, Yuchao Chen, Yuzhao Liu, Zhe Lei, Longqiang Wang, Hong-Tao Zhang, Xiangdong Li
Melatonin, an indolamine mostly synthesized in the pineal gland, exerts the anti-cancer effect by various mechanisms in glioma cells. Our previous study showed that miR-155 promoted glioma cell proliferation and invasion. However, the question of whether melatonin may inhibit glioma by regulating miRNAs has not yet been addressed. In this study, we found that melatonin (100μM, 1μM and 1nM) significantly inhibited the expression of miR-155 in human glioma cell lines U87, U373 and U251. Especially, the lowest expression of miR-155 was detected in 1μM melatonin-treated glioma cells...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28697743/integrative-analysis-of-copy-number-and-gene-expression-in-breast-cancer-using-formalin-fixed-paraffin-embedded-core-biopsy-tissue-a-feasibility-study
#8
Mahesh Iddawela, Oscar Rueda, Jenny Eremin, Oleg Eremin, Jed Cowley, Helena M Earl, Carlos Caldas
BACKGROUND: An absence of reliable molecular markers has hampered individualised breast cancer treatments, and a major limitation for translational research is the lack of fresh tissue. There are, however, abundant banks of formalin-fixed paraffin-embedded (FFPE) tissue. This study evaluated two platforms available for the analysis of DNA copy number and gene expression using FFPE samples. METHODS: The cDNA-mediated annealing, selection, extension, and ligation assay (DASL™) has been developed for gene expression analysis and the Molecular Inversion Probes assay (Oncoscan™), were used for copy number analysis using FFPE tissues...
July 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28675474/pherf6-interacting-with-eobi-negatively-regulates-fragrance-biosynthesis-in-petunia-flowers
#9
Fei Liu, Zhina Xiao, Li Yang, Qian Chen, Lu Shao, Juanxu Liu, Yixun Yu
In petunia, the production of volatile benzenoids/phenylpropanoids determines floral aroma, highly regulated by development, rhythm and ethylene. Previous studies identified several R2R3-type MYB trans-factors as positive regulators of scent biosynthesis in petunia flowers. Ethylene response factors (ERFs) have been shown to take part in the signal transduction of hormones, and regulation of metabolism and development processes in various plant species. Using virus-induced gene silencing technology, a negative regulator of volatile benzenoid biosynthesis, PhERF6, was identified by a screen for regulators of the expression of genes related to scent production...
September 2017: New Phytologist
https://www.readbyqxmd.com/read/28588701/aberrant-expression-of-aid-and-aid-activators-of-nf-%C3%AE%C2%BAb-and-pax5-is-irrelevant-to-ebv-associated-gastric-cancers-but-is-associated-with-carcinogenesis-in-certain-ebv-non-associated-gastric-cancers
#10
Takashi Mohri, Keiko Nagata, Satoshi Kuwamoto, Michiko Matsushita, Hirotsugu Sugihara, Masako Kato, Yasushi Horie, Ichiro Murakami, Kazuhiko Hayashi
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype of gastric cancer characterized by clinicopathological features including lymphoepithelioma-like histology. Aberrant expression of activation-induced cytidine deaminase (AID) as a genomic modulator was demonstrated through pathogen-related nuclear factor κB (NF-κB) signaling in Helicobacter pylori-associated gastric cancer. To elucidate whether or not AID expression is relevant to carcinogenesis in EBVaGC, immunohistochemical expression of AID and AID-regulatory factors between EBVaGC and EBV-non-associated gastric carcinoma (GC) were evaluated, each using 15 cases of GC with lymphoid stroma (GCLS) and other types of GC...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28536644/microrna-548c-3p-inhibits-t98g-glioma-cell-proliferation-and-migration-by-downregulating-c-myb
#11
Jianyi Lu, Min Zhang, Xiao Yang, Tong Cui, Jinpo Dai
MicroRNAs (miRNAs/miRs) are short non-coding RNAs (between 20 and 22 nucleotides) that regulate gene expression by binding to the 3'-untranslated region of target mRNA, and preventing protein translation or inducing mRNA destabilization. miRNAs are predicted to target ~60% of all mRNAs, therefore providing a marked degree of regulation of a number of cellular processes. In the present study, the expression of miR-548c-3p was determined by reverse transcription-quantitative polymerase chain reaction analysis and demonstrated to be markedly downregulated in clinical malignant glioma tissues and the glioma T98G cell line compared with normal human brain tissue...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28495617/the-adaptor-protein-ara55-and-the-nuclear-kinase-hipk1-assist-c-myb-in-recruiting-p300-to-chromatin
#12
Mads Bengtsen, Linda Sørensen, Linn Aabel, Marit Ledsaak, Vilborg Matre, Odd Stokke Gabrielsen
LIM-domain proteins, containing multiple cysteine-rich zinc finger-like motifs, have been shown to play diverse roles in several cellular processes. A common theme is that they mediate important protein-protein interactions that are key to their function. Androgen receptor-associated protein 55 (ARA55) belongs to this family of bridging proteins containing four C-terminal LIM domains. It has a dual role with functions both at focal adhesions and in the nucleus, apparently shuttling between the two compartments...
May 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28472346/a-c-myb-mutant-causes-deregulated-differentiation-due-to-impaired-histone-binding-and-abrogated-pioneer-factor-function
#13
Bettina M Fuglerud, Roza B Lemma, Pimthanya Wanichawan, Arvind Y M Sundaram, Ragnhild Eskeland, Odd S Gabrielsen
The transcription factor c-Myb is involved in early differentiation and proliferation of haematopoietic cells, where it operates as a regulator of self-renewal and multi-lineage differentiation. Deregulated c-Myb plays critical roles in leukaemias and other human cancers. Due to its role as a master regulator, we hypothesized it might function as a pioneer transcription factor. Our approach to test this was to analyse a mutant of c-Myb, D152V, previously reported to cause haematopoietic defects in mice by an unknown mechanism...
July 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28445549/impact-of-the-c-mybe308g-mutation-on-mouse-myelopoiesis-and-dendritic-cell-development
#14
Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill
Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct differentiation from HSPCs co-cultured over splenic stroma...
2017: PloS One
https://www.readbyqxmd.com/read/28423310/c-myb-regulates-the-t-bet-dependent-differentiation-program-in-b-cells-to-coordinate-antibody-responses
#15
Dana Piovesan, Jessica Tempany, Andrea Di Pietro, Inge Baas, Callisthenis Yiannis, Kristy O'Donnell, Yunshun Chen, Victor Peperzak, Gabrielle T Belz, Charles R Mackay, Gordon K Smyth, Joanna R Groom, David M Tarlinton, Kim L Good-Jacobson
Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28404913/a-novel-role-of-ckip-1-in-promoting-megakaryocytic-differentiation
#16
Jiao Fan, Yiwu Wang, Yuan Shen, Qingyan Liu, Rong Gao, Ya Qiu, Chanjuan Wang, Lingqiang Zhang
Casein kinase 2-interacting protein-1 (CKIP-1) is a known regulator of cardiomyocytes and macrophage proliferation. In this study, we showed that CKIP-1 was involved in the process of megakaryocytic differentiation. During megakaryocytic differentiation of K562 cells, CKIP-1 was dramatically upregulated and this upregulation induced by PMA was mediated through downregulation of transcription factor GATA-1. By transient transfection, oligonucleotide-directed mutagenesis and chromatin immunoprecipitation assays, we identified the transcriptional regulation of CKIP-1 by GATA-1...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28373291/dual-mechanism-of-rag-gene-repression-by-c-myb-during-pre-b-cell-proliferation
#17
Greg A Timblin, Liangqi Xie, Robert Tjian, Mark S Schlissel
Developing B lymphocytes undergo clonal expansion following successful immunoglobulin heavy chain gene rearrangement. During this proliferative burst, expression of the Rag genes is transiently repressed to prevent the generation of double-stranded DNA (dsDNA) breaks in cycling large pre-B cells. The Rag genes are then reexpressed in small, resting pre-B cells for immunoglobulin light chain gene rearrangement. We previously identified c-Myb as a repressor of Rag transcription during clonal expansion using Abelson murine leukemia virus-transformed B cells...
June 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28361042/sodium-octanoate-modulates-the-innate-immune-response-of-bovine-mammary-epithelial-cells-through-the-tlr2-p38-jnk-erk1-2-pathway-implications-during-staphylococcus-aureus-internalization
#18
Nayeli Alva-Murillo, Alejandra Ochoa-Zarzosa, Joel E López-Meza
Bovine mammary epithelial cells (bMECs) contribute to mammary gland defense against invading pathogens, such as Staphylococcus aureus (intracellular facultative), which is recognized by TLR2. In a previous report, we showed that sodium octanoate [NaO, a medium chain fatty acid (C8)] induces (0.25 mM) or inhibits (1 mM) S. aureus internalization into bMECs and differentially regulates the innate immune response (IIR). However, the molecular mechanisms have not been described, which was the aim of this study...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28330872/nadph-oxidase-1-supports-proliferation-of-colon-cancer-cells-by-modulating-reactive-oxygen-species-dependent-signal-transduction
#19
Agnes Juhasz, Susan Markel, Shikha Gaur, Han Liu, Jiamo Lu, Guojian Jiang, Xiwei Wu, Smitha Antony, Yongzhong Wu, Giovanni Melillo, Jennifer L Meitzler, Diana C Haines, Donna Butcher, Krishnendu Roy, James H Doroshow
Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates O2(̇̄), is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80-90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G1/S block that translated into a 2-3-fold increase in tumor cell doubling time without increased apoptosis...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28244490/the-rna-binding-protein-qki5-regulates-primary-mir-124-1-processing-via-a-distal-rna-motif-during-erythropoiesis
#20
Fang Wang, Wei Song, Hongmei Zhao, Yanni Ma, Yuxia Li, Di Zhai, Jingnan Pi, Yanmin Si, Jiayue Xu, Lei Dong, Rui Su, Mengmeng Zhang, Yong Zhu, Xiaoxia Ren, Fei Miao, Wenjie Liu, Feng Li, Junwu Zhang, Aibin He, Ge Shan, Jingyi Hui, Linfang Wang, Jia Yu
MicroRNA (miRNA) biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins (RBPs). Here, we show that an RBP, QKI5, activates the processing of primary miR-124-1 (pri-124-1) during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCR8. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation...
March 2017: Cell Research
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