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Cell Reports

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https://www.readbyqxmd.com/read/30110647/differential-hdac6-activity-modulates-ciliogenesis-and-subsequent-mechanosensing-of-endothelial-cells-derived-from-pluripotent-stem-cells
#1
Quinton Smith, Bria Macklin, Xin Yi Chan, Hannah Jones, Michelle Trempel, Mervin C Yoder, Sharon Gerecht
No abstract text is available yet for this article.
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110646/proteomic-characterization-of-the-heart-and-skeletal-muscle-reveals-widespread-arginine-adp-ribosylation-by-the-artc1-ectoenzyme
#2
Mario Leutert, Stephan Menzel, Rickmer Braren, Björn Rissiek, Ann-Katrin Hopp, Kathrin Nowak, Lavinia Bisceglie, Peter Gehrig, Hui Li, Anna Zolkiewska, Friedrich Koch-Nolte, Michael O Hottiger
The clostridium-like ecto-ADP-ribosyltransferase ARTC1 is expressed in a highly restricted manner in skeletal muscle and heart tissue. Although ARTC1 is well studied, the identification of ARTC1 targets in vivo and subsequent characterization of ARTC1-regulated cellular processes on the proteome level have been challenging and only a few ARTC1-ADP-ribosylated targets are known. Applying our recently developed mass spectrometry-based workflow to C2C12 myotubes and to skeletal muscle and heart tissues from wild-type mice, we identify hundreds of ARTC1-ADP-ribosylated proteins whose modifications are absent in the ADP-ribosylome of ARTC1-deficient mice...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110645/large-scale-human-dendritic-cell-differentiation-revealing-notch-dependent-lineage-bifurcation-and-heterogeneity
#3
Sreekumar Balan, Catharina Arnold-Schrauf, Abdenour Abbas, Norbert Couespel, Juliette Savoret, Francesco Imperatore, Alexandra-Chloé Villani, Thien-Phong Vu Manh, Nina Bhardwaj, Marc Dalod
The ability to generate large numbers of distinct types of human dendritic cells (DCs) in vitro is critical for accelerating our understanding of DC biology and harnessing them clinically. We developed a DC differentiation method from human CD34+ precursors leading to high yields of plasmacytoid DCs (pDCs) and both types of conventional DCs (cDC1s and cDC2s). The identity of the cells generated in vitro and their strong homology to their blood counterparts were demonstrated by phenotypic, functional, and single-cell RNA-sequencing analyses...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110644/identification-biosynthesis-and-decapping-of-nad-capped-rnas-in-b-subtilis
#4
Jens Frindert, Yaqing Zhang, Gabriele Nübel, Masroor Kahloon, Leonie Kolmar, Agnes Hotz-Wagenblatt, Jürgen Burhenne, Walter E Haefeli, Andres Jäschke
The ubiquitous coenzyme nicotinamide adenine dinucleotide (NAD) decorates various RNAs in different organisms. In the proteobacterium Escherichia coli, the NAD-cap confers stability against RNA degradation. To date, NAD-RNAs have not been identified in any other bacterial microorganism. Here, we report the identification of NAD-RNA in the firmicute Bacillus subtilis. In the late exponential growth phase, predominantly mRNAs are NAD modified. NAD is incorporated de novo into RNA by the cellular RNA polymerase using non-canonical transcription initiation...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110643/the-c-elegans-brca2-alp-enigma-complex-regulates-axon-regeneration-via-a-rho-gtpase-rock-mlc-phosphorylation-pathway
#5
Tatsuhiro Shimizu, Strahil Iv Pastuhov, Hiroshi Hanafusa, Kunihiro Matsumoto, Naoki Hisamoto
The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the mechanisms regulating axon regeneration are not well understood. Here, we identify the brc-2 gene encoding a homolog of the mammalian BRCA2 tumor suppressor as a regulator of axon regeneration in Caenorhabditis elegans motor neurons. We show that the RHO-1/Rho GTPase-LET-502/ROCK (Rho-associated coiled-coil kinase)-regulatory non-muscle myosin light-chain (MLC-4/MLC) phosphorylation signaling pathway regulates axon regeneration...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110642/neuronal-specific-tubb3-is-not-required-for-normal-neuronal-function-but-is-essential-for-timely-axon-regeneration
#6
Alban Latremoliere, Long Cheng, Michelle DeLisle, Chen Wu, Sheena Chew, Elizabeth B Hutchinson, Andrew Sheridan, Chloe Alexandre, Frederic Latremoliere, Shu-Hsien Sheu, Sara Golidy, Takao Omura, Eric A Huebner, Yanjie Fan, Mary C Whitman, Elaine Nguyen, Crystal Hermawan, Carlo Pierpaoli, Max A Tischfield, Clifford J Woolf, Elizabeth C Engle
We generated a knockout mouse for the neuronal-specific β-tubulin isoform Tubb3 to investigate its role in nervous system formation and maintenance. Tubb3-/- mice have no detectable neurobehavioral or neuropathological deficits, and upregulation of mRNA and protein of the remaining β-tubulin isotypes results in equivalent total β-tubulin levels in Tubb3-/- and wild-type mice. Despite similar levels of total β-tubulin, adult dorsal root ganglia lacking TUBB3 have decreased growth cone microtubule dynamics and a decreased neurite outgrowth rate of 22% in vitro and in vivo...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110641/maf1-and-repression-of-rna-polymerase-iii-mediated-transcription-drive-adipocyte-differentiation
#7
Chun-Yuan Chen, Rainer B Lanz, Christopher J Walkey, Wen-Hsuan Chang, Wange Lu, Deborah L Johnson
RNA polymerase (pol) III transcribes a variety of small untranslated RNAs involved in transcription, RNA processing, and translation. RNA pol III and its components are altered in various human developmental disorders, yet their roles in cell fate determination and development are poorly understood. Here we demonstrate that Maf1, a transcriptional repressor, promotes induction of mouse embryonic stem cells (mESCs) into mesoderm. Reduced Maf1 expression in mESCs and preadipocytes impairs adipogenesis, while ectopic Maf1 expression in Maf1-deficient cells enhances differentiation...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110640/orthogonal-dietary-niche-enables-reversible-engraftment-of-a-gut-bacterial-commensal
#8
Sean M Kearney, Sean M Gibbons, Susan E Erdman, Eric J Alm
Interest in manipulating the gut microbiota to treat disease has led to a need for understanding how organisms can establish themselves when introduced into a host with an intact microbial community. Here, we employ the concept of orthogonal niche engineering: a resource typically absent from the diet, seaweed, creates a customized niche for an introduced organism. In the short term, co-introduction of this resource at 1% in the diet along with an organism with exclusive access to this resource, Bacteroides plebeius DSM 17135, enables it to colonize at a median abundance of 1% and frequently up to 10 or more percent, both on pulsed and constant seaweed diets...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110639/lnk-sh2b3-regulates-adipose-inflammation-and-glucose-tolerance-through-group-1-ilcs
#9
Taizo Mori, Nao Suzuki-Yamazaki, Satoshi Takaki
Lnk/Sh2b3 is an adaptor protein that negatively regulates cytokine signaling in lymphohematopoiesis. A missense variant within the LNK/SH2B3 gene has been reported to be a risk variant for several autoimmune diseases, including diabetes. We found that glucose tolerance and insulin responses were impaired in Lnk-/- mice. Moreover, immune cells such as group 1 innate lymphoid cells (G1-ILCs), CD8+ T cells, and M1 macrophages accumulated in adipose tissue. When Lnk-/- mice were crossed with Il15-/- mice or depleted of G1-ILCs but not CD8+ T cells, glucose intolerance and adipose inflammation were ameliorated...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110638/antibody-repertoires-to-the-same-ebola-vaccine-antigen-are-differentially-affected-by-vaccine-vectors
#10
Michelle Meyer, Asuka Yoshida, Palaniappan Ramanathan, Erica Ollmann Saphire, Peter L Collins, James E Crowe, Siba Samal, Alexander Bukreyev
Comparative immune response profiling is important for selecting next-generation vaccines. We comprehensively evaluated the antibody responses from a panel of nine respiratory vaccines against Ebola virus (EBOV) derived from human and avian paramyxoviruses expressing EBOV glycoprotein (GP). Most vaccines were protective in guinea pigs but yielded antibody repertoires that differed in proportion targeting key antigenic regions, avidity, neutralizing antibody specificities, and linear epitope preferences. Competition studies with monoclonal antibodies from human survivors revealed that some epitopes in GP targeted for neutralization were vector dependent, while EBOV-neutralizing titers correlated with the response magnitude toward the receptor-binding domain and GP1/GP2 interface epitopes...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110637/antibody-dependent-enhancement-of-ebola-virus-infection-by-human-antibodies-isolated-from-survivors
#11
Natalia A Kuzmina, Patrick Younan, Pavlo Gilchuk, Rodrigo I Santos, Andrew I Flyak, Philipp A Ilinykh, Kai Huang, Ndongala M Lubaki, Palaniappan Ramanathan, James E Crowe, Alexander Bukreyev
Some monoclonal antibodies (mAbs) recovered from survivors of filovirus infections can protect against infection. It is currently unknown whether natural infection also induces some antibodies with the capacity for antibody-dependent enhancement (ADE). A panel of mAbs obtained from human survivors of filovirus infection caused by Ebola, Bundibugyo, or Marburg viruses was evaluated for their ability to facilitate ADE. ADE was observed readily with all mAbs examined at sub-neutralizing concentrations, and this effect was not restricted to mAbs with a particular epitope specificity, neutralizing capacity, or subclass...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110636/blocking-the-fstl1-dip2a-axis-improves-anti-tumor-immunity
#12
Chie Kudo-Saito, Akiko Ishida, Yuji Shouya, Koji Teramoto, Tomoyuki Igarashi, Ryoko Kon, Kenji Saito, Chihiro Awada, Yamato Ogiwara, Masayoshi Toyoura
Immune dysfunction is a strong factor in the resistance of cancer to treatment. Blocking immune checkpoint pathways is a promising approach to improve anti-tumor immunity, but the clinical efficacies are still limited. We previously identified follistatin-like 1 (FSTL1) as a determinant of immune dysfunction mediated by mesenchymal stromal/stem cells (MSCs) and immunoregulatory cells. Here, we demonstrate that blocking FSTL1 but not immune checkpoint pathways significantly suppresses cancer progression and metastasis in several mouse tumor models with increased MSCs...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110635/clonal-expansion-and-diversification-of-cancer-associated-mutations-in-endometriosis-and-normal-endometrium
#13
Kazuaki Suda, Hirofumi Nakaoka, Kosuke Yoshihara, Tatsuya Ishiguro, Ryo Tamura, Yutaro Mori, Kaoru Yamawaki, Sosuke Adachi, Tomoko Takahashi, Hiroaki Kase, Kenichi Tanaka, Tadashi Yamamoto, Teiichi Motoyama, Ituro Inoue, Takayuki Enomoto
Endometriosis is characterized by ectopic endometrial-like epithelium and stroma, of which molecular characteristics remain to be fully elucidated. We sequenced 107 ovarian endometriotic and 82 normal uterine endometrial epithelium samples isolated by laser microdissection. In both endometriotic and normal epithelium samples, numerous somatic mutations were identified within genes frequently mutated in endometriosis-associated ovarian cancers. KRAS is frequently mutated in endometriotic epithelium, with a higher mutant allele frequency (MAF) accompanied by arm-level allelic imbalances...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110634/a-zombie-lif-gene-in-elephants-is-upregulated-by-tp53-to-induce-apoptosis-in-response-to-dna-damage
#14
Juan Manuel Vazquez, Michael Sulak, Sravanthi Chigurupati, Vincent J Lynch
Large-bodied organisms have more cells that can potentially turn cancerous than small-bodied organisms, imposing an increased risk of developing cancer. This expectation predicts a positive correlation between body size and cancer risk; however, there is no correlation between body size and cancer risk across species ("Peto's paradox"). Here, we show that elephants and their extinct relatives (proboscideans) may have resolved Peto's paradox in part through refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110633/resolving-escrt-iii-spirals-at-the-intercellular-bridge-of-dividing-cells-using-3d-storm
#15
Inna Goliand, Shai Adar-Levor, Inbar Segal, Dikla Nachmias, Tali Dadosh, Michael M Kozlov, Natalie Elia
The ESCRT machinery mediates membrane fission in a variety of processes in cells. According to current models, ESCRT-III proteins drive membrane fission by assembling into helical filaments on membranes. Here, we used 3D STORM imaging of endogenous ESCRT-III component IST1 to reveal the evolution of the structural organization of ESCRT-III in mammalian cytokinetic abscission. Using this approach, ESCRT-III ring and spiral assemblies were resolved and characterized at different stages of abscission. Visualization of IST1 structures in cells lacking the microtubule-severing enzyme spastin and in cells depleted of specific ESCRT-III components or the ATPase VPS4 demonstrated the contribution of these components to the organization and function of ESCRTs in cells...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110632/runx-poly-adp-ribosyl-ation-and-blm-interaction-facilitate-the-fanconi-anemia-pathway-of-dna-repair
#16
Lavina Sierra Tay, Vaidehi Krishnan, Haresh Sankar, Yu Lin Chong, Linda Shyue Huey Chuang, Tuan Zea Tan, Arun Mouli Kolinjivadi, Dennis Kappei, Yoshiaki Ito
The Fanconi anemia (FA) pathway is a pivotal genome maintenance network that orchestrates the repair of DNA interstrand crosslinks (ICLs). The tumor suppressors RUNX1 and RUNX3 were shown to regulate the FA pathway independent of their canonical transcription activities, by controlling the DNA damage-dependent chromatin association of FANCD2. Here, in further biochemical characterization, we demonstrate that RUNX3 is modified by PARP-dependent poly(ADP-ribosyl)ation (PARylation), which in turn allows RUNX binding to DNA repair structures lacking transcription-related RUNX consensus motifs...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110631/von-hippel-lindau-protein-is-required-for-optimal-alveolar-macrophage-terminal-differentiation-self-renewal-and-function
#17
Helena M Izquierdo, Paola Brandi, Manuel-José Gómez, Ruth Conde-Garrosa, Elena Priego, Michel Enamorado, Sarai Martínez-Cano, Iria Sánchez, Laura Conejero, Daniel Jimenez-Carretero, Silvia Martín-Puig, Martin Guilliams, David Sancho
The rapid transit from hypoxia to normoxia in the lung that follows the first breath in newborn mice coincides with alveolar macrophage (AM) differentiation. However, whether sensing of oxygen affects AM maturation and function has not been previously explored. We have generated mice whose AMs show a deficient ability to sense oxygen after birth by deleting Vhl, a negative regulator of HIF transcription factors, in the CD11c compartment (CD11cΔVhl mice). VHL-deficient AMs show an immature-like phenotype and an impaired self-renewal capacity in vivo that persists upon culture ex vivo...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110630/adaptive-evolution-of-mers-cov-to-species-variation-in-dpp4
#18
Michael Letko, Kerri Miazgowicz, Rebekah McMinn, Stephanie N Seifert, Isabel Sola, Luis Enjuanes, Aaron Carmody, Neeltje van Doremalen, Vincent Munster
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110629/enhancer-activity-requires-cbp-p300-bromodomain-dependent-histone-h3k27-acetylation
#19
Ryan Raisner, Samir Kharbanda, Lingyan Jin, Edwin Jeng, Emily Chan, Mark Merchant, Peter M Haverty, Russell Bainer, Tommy Cheung, David Arnott, E Megan Flynn, F Anthony Romero, Steven Magnuson, Karen E Gascoigne
Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (CREB) binding protein (CBP)/P300 bromodomain in models of hematological malignancies and describe a consequent loss of H3K27Ac specifically from enhancers, despite the continued presence of CBP/P300 at chromatin. Using this approach to dissect the role of H3K27Ac at enhancers, we identify a critical role for this modification in the production of enhancer RNAs and transcription of enhancer-regulated gene networks...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30110628/stress-induced-low-complexity-rna-activates-physiological-amyloidogenesis
#20
Miling Wang, Xianzun Tao, Mathieu D Jacob, Clayton A Bennett, J J David Ho, Mark L Gonzalgo, Timothy E Audas, Stephen Lee
Amyloid bodies (A-bodies) are inducible membrane-less nuclear compartments composed of heterogeneous proteins that adopt an amyloid-like state. A-bodies are seeded by noncoding RNA derived from stimuli-specific loci of the rDNA intergenic spacer (rIGSRNA). This raises the question of how rIGSRNA recruits a large population of diverse proteins to confer A-body identity. Here, we show that long low-complexity dinucleotide repeats operate as the architectural determinants of rIGSRNA. On stimulus, clusters of rIGSRNA with simple cytosine/uracil (CU) or adenosine/guanine (AG) repeats spanning hundreds of nucleotides accumulate in the nucleolar area...
August 14, 2018: Cell Reports
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