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dendrite RNA

Michael J Ziller, Juan A Ortega, Katharina A Quinlan, David P Santos, Hongcang Gu, Eric J Martin, Christina Galonska, Ramona Pop, Susanne Maidl, Alba Di Pardo, Mei Huang, Herbert Y Meltzer, Andreas Gnirke, C J Heckman, Alexander Meissner, Evangelos Kiskinis
The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing...
March 14, 2018: Cell Stem Cell
Gaetan Barbet, Leif E Sander, Matthew Geswell, Irina Leonardi, Andrea Cerutti, Iliyan Iliev, J Magarian Blander
Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses...
March 9, 2018: Immunity
Clément Cochain, Ehsan Vafadarnejad, Panagiota Arampatzi, Pelisek Jaroslav, Holger Winkels, Klaus Ley, Dennis Wolf, Antoine-Emmanuel Saliba, Alma Zernecke
<u>Rationale:</u> It is assumed that atherosclerotic arteries contain several macrophage subsets endowed with specific functions. The precise identity of these subsets is poorly characterized as they ha ve been defined by the expression of a restricted number of markers. <u>Objective:</u> We have applied single-cell RNA-seq as an unbiased profiling strategy to interrogate and classify aortic macrophage heterogeneity at the single-cell level in atherosclerosis. <u>Methods and Results:</u> We performed single-cell RNA sequencing of total aortic CD45+ cells extracted from the non-diseased (chow fed) and atherosclerotic (11 weeks of high fat diet) aorta of Ldlr-/- mice...
March 15, 2018: Circulation Research
Atsuko Kayaba, Ari Itoh-Nakadai, Kunimichi Niibe, Matsuyuki Shirota, Ryo Funayama, Akiko Sugahara-Tobinai, Yi Li Wong, Masanori Inui, Keiko Nakayama, Toshiyuki Takai
Plasma cells (PCs) acquiring with long lives in bone marrow (BM) play a pivotal role in the humoral arm of immunological memory. The PCs reside in a special BM niche and produce antibodies against past-encountered pathogens or vaccine components for a long time. In BM, cysteine-X-cysteine (CXC) chemokine receptor type 4-expressing PCs and myeloid cells such as dendritic cells are attracted to and held by CXC chemokine ligand 12-secreting stromal cells, where survival of the PCs is supported by soluble factors such as IL-6 and a proliferation-inducing ligand or APRIL produced by neighboring myeloid cells...
February 24, 2018: International Immunology
Matthew C Altman, Elizabeth Whalen, Alkis Togias, George T O'Connor, Leonard B Bacharier, Gordon R Bloomberg, Meyer Kattan, Robert A Wood, Scott Presnell, Petra LeBeau, Katy Jaffee, Cynthia M Visness, William W Busse, James E Gern
BACKGROUND: Childhood asthma in inner city populations is a major public health burden and understanding early life immune mechanisms that promote asthma onset is key to disease prevention. Children who develop asthma demonstrate a high prevalence of aeroallergen sensitization and T helper 2 (Th2)-type inflammation, however the early life immune events that lead to Th2 skewing and disease development are unknown. OBJECTIVE: We sought to use RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected at age 2 to determine networks of immune responses that occur in children who develop allergy and asthma...
March 5, 2018: Journal of Allergy and Clinical Immunology
Sumito Yoshida, Hiroaki Shime, Yohei Takeda, Jin-Min Nam, Ken Takashima, Misako Matsumoto, Hiroki Shirato, Masanori Kasahara, Tsukasa Seya
Radiotherapy induces anti-tumor immunity by induction of tumor antigens and damage-associated molecular patterns (DAMPs). DNA, a representative DAMP in radiotherapy, activates the STING pathway which enhances the immune response. However, the immune response does not always parallel the inflammation associated with radiotherapy. This lack of correspondence may in part explain the radiation-resistance of tumors. Additive immunotherapy is expected to revive tumor-specific CTLs facilitating radiation-resistant tumor shrinkage...
February 21, 2018: Cancer Science
Christine E Beattie, Stephen J Kolb
Spinal muscular atrophy is caused by deletions or mutations in the SMN1 gene that result in reduced expression of the SMN protein. The SMN protein is an essential molecular chaperone that is required for the biogenesis of multiple ribonucleoprotein (RNP) complexes including spliceosomal small nuclear RNPs (snRNPs). Reductions in SMN expression result in a reduced abundance of snRNPs and to downstream RNA splicing alterations. SMN is also present in axons and dendrites and appears to have important roles in the formation of neuronal mRNA-protein complexes during development or neuronal repair...
February 17, 2018: Brain Research
Bilal Khalil, Dmytro Morderer, Phillip L Price, Feilin Liu, Wilfried Rossoll
The development, maturation, and maintenance of the mammalian nervous system rely on complex spatiotemporal patterns of gene expression. In neurons, this is achieved by the expression of differentially localized isoforms and specific sets of mRNA-binding proteins (mRBPs) that regulate RNA processing, mRNA trafficking, and local protein synthesis at remote sites within dendrites and axons. There is growing evidence that axons contain a specialized transcriptome and are endowed with the machinery that allows them to rapidly alter their local proteome via local translation and protein degradation...
February 17, 2018: Brain Research
Y L Wu, F Wu, L Yang, H Sun, X C Yan, G J Duan
Objective: To investigate the clinicopathological features and prognostic parameters of the inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) of liver and spleen. Methods: Ninteen cases of inflammatory pseudotumor (IPT) and 5 cases of IPT-like FDCS of the liver and spleen were collected at the First Affiliated Hospital, Army Medical University from 2006 to 2016. HE sections, immunohistochemical staining, and Epstein-Barr virus encoded nuclear RNA (EBER) in situ hybridization were reviewed along with a summary of the literature...
February 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
B Zhao, S Zhang, W Chen, R Zhang, R Jiang, R Zhang, L Chen
BACKGROUND & OBJECTIVE: Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS: 15 patients with HLA-B27-associated AAU, 10 patients with idiopathic AAU and 22 controls were recruited to this study from August 2013 to December 2016...
February 7, 2018: Current Molecular Medicine
Matthew P Bronnimann, Pamela J Skinner, Elizabeth Connick
The majority of HIV replication occurs in secondary lymphoid organs (SLOs) such as the spleen, lymph nodes, and gut-associated lymphoid tissue. Within SLOs, HIV RNA+ cells are concentrated in the B-cell follicle during chronic untreated infection, and emerging data suggest that they are a major source of replication in treated disease as well. The concentration of HIV RNA+ cells in the B-cell follicle is mediated by several factors. Follicular CD4+ T-cell subsets including T-follicular helper cells and T-follicular regulatory cells are significantly more permissive to HIV than extrafollicular subsets...
2018: Frontiers in Immunology
Tadaomi Kawashima, Naho Ikari, Yohei Watanabe, Yoshiro Kubota, Sachiyo Yoshio, Tatsuya Kanto, Shinichiro Motohashi, Naoki Shimojo, Noriko M Tsuji
Lactic acid bacteria (LAB) are one of the major commensal species in the small intestine and known for contributing to maintenance of protective immunity and immune homeostasis. However, currently there has been no evidence regarding the cellular mechanisms involved in the probiotic effects of LAB on human immune cells. Here, we demonstrated that LAB double-stranded RNA (dsRNA) triggered interferon-β (IFN-β) production by human dendritic cells (DCs), which activated IFN-γ-producing T cells. Interleukin-12 (IL-12) secretion from human DCs in response to LAB was abrogated by depletion of bacterial dsRNA, and was attenuated by neutralizing IFN-β, indicating LAB dsRNA primarily activated the IFN-β/IL-12 pathway...
2018: Frontiers in Immunology
Carly A Dillen, Bret L Pinsker, Alina I Marusina, Alexander A Merleev, Orly N Farber, Haiyun Liu, Nathan K Archer, Da B Lee, Yu Wang, Roger V Ortines, Steven K Lee, Mark C Marchitto, Shuting S Cai, Alyssa G Ashbaugh, Larissa S May, Steven M Holland, Alexandra F Freeman, Loren G Miller, Michael R Yeaman, Scott I Simon, Joshua D Milner, Emanual Maverakis, Lloyd S Miller
The mechanisms that mediate durable protection against Staphylococcus aureus skin reinfections are unclear, as recurrences are common despite high antibody titers and memory T cells. Here, we developed a mouse model of S. aureus skin reinfection to investigate protective memory responses. In contrast with WT mice, IL-1β-deficient mice exhibited poor neutrophil recruitment and bacterial clearance during primary infection that was rescued during secondary S. aureus challenge. The γδ T cells from skin-draining LNs utilized compensatory T cell-intrinsic TLR2/MyD88 signaling to mediate rescue by trafficking and producing TNF and IFN-γ, which restored neutrophil recruitment and promoted bacterial clearance...
February 5, 2018: Journal of Clinical Investigation
Irina Obleukhova, Nataliya Kiryishina, Svetlana Falaleeva, Julia Lopatnikova, Vasiliy Kurilin, Vadim Kozlov, Aleksander Vitsin, Andrey Cherkasov, Ekaterina Kulikova, Sergey Sennikov
Cancer is associated with a reduction in immature and mature circulating dendritic cells (DCs), and with an impaired migratory capacity, compared with healthy donors. Therefore, modern approaches to the in vitro generation of DCs loaded with tumor antigens and their use for inducing antitumor immune responses in vivo are being investigated. The purpose of the present study was to investigate the phenotypic and functional characteristics of peripheral blood DC subsets in patients with non-small cell lung cancer (NSCLC), and the development of an antitumor cytotoxic response by mononuclear cells (MNCs) from patients using in vitro generated antigen-primed DCs...
January 2018: Oncology Letters
Chhavi Mathur, Kory R Johnson, Brian A Tong, Pablo Miranda, Deepa Srikumar, Daniel Basilio, Ramon Latorre, Francisco Bezanilla, Miguel Holmgren
Local translation of membrane proteins in neuronal subcellular domains like soma, dendrites and axon termini is well-documented. In this study, we isolated the electrical signaling unit of an axon by dissecting giant axons from mature squids (Dosidicus gigas). Axoplasm extracted from these axons was found to contain ribosomal RNAs, ~8000 messenger RNA species, many encoding the translation machinery, membrane proteins, translocon and signal recognition particle (SRP) subunits, endomembrane-associated proteins, and unprecedented proportions of SRP RNA (~68% identical to human homolog)...
February 2, 2018: Scientific Reports
Qi Li, Xiaohong Peng, Haoran Huang, Jingjing Li, Fan Wang, Jie Wang
This study aimed to identify miRNAs that may contribute to the pathogenesis of sudden sensorineural hearing loss (SSNHL) by RNA-seq (RNA-sequencing).RNA was extracted from SSNHL patients and healthy volunteers, respectively. Sequencing was performed on HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differential expression analysis of miRNAs between the SSNHL samples and the normal samples was performed using DEseq to identify differentially expressed microRNAs (DEMs)...
November 2017: Medicine (Baltimore)
Kristin Michaelsen-Preusse, Jonas Feuge, Martin Korte
Our experiences and memories define who we are and evidence accumulates that memory formation is dependent on functional and structural adaptations of synaptic structures in our brain. Especially dendritic spines, the postsynaptic compartments of synapses, show a strong structure-to-function relationship and a high degree of structural plasticity. Although the molecular mechanisms are not completely understood, it is known that these modifications are highly dependent on the actin-cytoskeleton, the major cytoskeletal component of the spine...
January 30, 2018: Journal of Physiology
Enrique Martin-Gayo, Michael B Cole, Kellie E Kolb, Zhengyu Ouyang, Jacqueline Cronin, Samuel W Kazer, Jose Ordovas-Montanes, Mathias Lichterfeld, Bruce D Walker, Nir Yosef, Alex K Shalek, Xu G Yu
BACKGROUND: Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. RESULTS: To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification...
January 29, 2018: Genome Biology
Xuemei Chen, Patricia Elena Kunda, Jianwei Lin, Meiling Zhou, Jinghan Huang, Huqin Zhang, Tao Liu
PURPOSE: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemotherapy is currently the main method of RB treatment. Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in vitro cell immunotherapy to explore whether adoptive immunotherapy could be used as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK), which is significantly upregulated in RB cells and serves as a marker for RB cells. METHODS: Using lentiviruses, we genetically modified dendritic cells (DCs) to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs) in vitro...
January 25, 2018: Journal of Cancer Research and Clinical Oncology
Lianghua Bin, Xiaozhao Li, Brittany Richers, Joanne E Streib, Jack W Hu, Patricia Taylor, Donald Y M Leung
BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease. A subset of AD is susceptible to disseminated herpes simplex virus (HSV) infection, a complication termed as eczema herpeticum(ADEH+). The immune mechanisms causing ADEH+ remain elusive. Using RNA-sequencing, we recently found that ankyrin repeat domain 1 (ANKRD1) was significantly induced in human peripheral blood mononuclear cells (PBMCs) upon HSV-1 stimulation; and its induction in ADEH+ was significantly reduced as compared to AD patients without a history of EH (ADEH-)...
January 22, 2018: Journal of Allergy and Clinical Immunology
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