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Cell Reports

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https://www.readbyqxmd.com/read/30509557/regional-control-of-hairless-versus-hair-bearing-skin-by-dkk2
#1
Yaolin Song, Ana C Boncompagni, Sang-Seok Kim, Heather R Gochnauer, Yuhang Zhang, Gabriela G Loots, Dianqing Wu, Yulin Li, Mingang Xu, Sarah E Millar
Haired skin is a defining characteristic of mammals. However, some specialized skin regions, such as human palms, soles and ventral wrist, and mouse plantar foot, are entirely hairless. Using mouse plantar skin as a model system, we show that the endogenous secreted Wnt inhibitor DKK2 suppresses plantar hair follicle development and permits the formation of hairless skin. Plantar skin retains all of the mechanistic components needed for hair follicle development, as genetic deletion of Dkk2 permits formation of fully functional plantar hair follicles that give rise to external hair, contain sebaceous glands and a stem cell compartment, and undergo regenerative growth...
November 29, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517876/development-and-application-of-fasa-a-model-for-quantifying-fatty-acid-metabolism-using-stable-isotope-labeling
#2
Joseph P Argus, Moses Q Wilks, Quan D Zhou, Wei Yuan Hsieh, Elvira Khialeeva, Xen Ping Hoi, Viet Bui, Shili Xu, Amy K Yu, Eric S Wang, Harvey R Herschman, Kevin J Williams, Steven J Bensinger
It is well understood that fatty acids can be synthesized, imported, and modified to meet requisite demands in cells. However, following the movement of fatty acids through the multiplicity of these metabolic steps has remained difficult. To better address this problem, we developed Fatty Acid Source Analysis (FASA), a model that defines the contribution of synthesis, import, and elongation pathways to fatty acid homeostasis in saturated, monounsaturated, and polyunsaturated fatty acid pools. Application of FASA demonstrated that elongation can be a major contributor to cellular fatty acid content and showed that distinct pro-inflammatory stimuli (e...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517875/integrated-in-vivo-quantitative-proteomics-and-nutrient-tracing-reveals-age-related-metabolic-rewiring-of-pancreatic-%C3%AE-cell-function
#3
Matthew Wortham, Jacqueline R Benthuysen, Martina Wallace, Jeffrey N Savas, Francesca Mulas, Ajit S Divakaruni, Fenfen Liu, Verena Albert, Brandon L Taylor, Yinghui Sui, Enrique Saez, Anne N Murphy, John R Yates, Christian M Metallo, Maike Sander
Pancreatic β cell physiology changes substantially throughout life, yet the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivo quantitative proteomic profiling of pancreatic islets from juvenile and 1-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517874/madid-a-versatile-approach-to-map-protein-dna-interactions-highlights-telomere-nuclear-envelope-contact-sites-in-human-cells
#4
Michal Sobecki, Charbel Souaid, Jocelyne Boulay, Vincent Guerineau, Daan Noordermeer, Laure Crabbe
Mapping the binding sites of DNA- or chromatin-interacting proteins is essential to understanding biological processes. DNA adenine methyltransferase identification (DamID) has emerged as a comprehensive method to map genome-wide occupancy of proteins of interest. A caveat of DamID is the specificity of Dam methyltransferase for GATC motifs that are not homogenously distributed in the genome. Here, we developed an optimized method named MadID, using proximity labeling of DNA by the methyltransferase M.EcoGII...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517873/ulk1-o-glcnacylation-is-crucial-for-activating-vps34-via-atg14l-during-autophagy-initiation
#5
Ki Eun Pyo, Chang Rok Kim, Minkyoung Lee, Jong-Seo Kim, Keun Il Kim, Sung Hee Baek
Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation. Upon glucose starvation, dissociation of mTOR from ULK1 and phosphorylation by AMPK leads to the activation of ULK1 activity. Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517872/csap-acts-as-a-regulator-of-ttll-mediated-microtubule-glutamylation
#6
Guillaume Bompard, Juliette van Dijk, Julien Cau, Yoann Lannay, Guillaume Marcellin, Aleksandra Lawera, Siem van der Laan, Krzysztof Rogowski
Tubulin glutamylation is a reversible posttranslational modification that accumulates on stable microtubules (MTs). While abnormally high levels of this modification lead to a number of disorders such as male sterility, retinal degeneration, and neurodegeneration, very little is known about the molecular mechanisms underlying the regulation of glutamylase activity. Here, we found that CSAP forms a complex with TTLL5, and we demonstrate that the two proteins regulate their reciprocal abundance. Moreover, we show that CSAP increases TTLL5-mediated glutamylation and identify the TTLL5-interacting domain...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517871/histone-deacetylase-sirt1-targets-plk2-to-regulate-centriole-duplication
#7
Hongbo Ling, Lirong Peng, Jianbo Wang, Raneen Rahhal, Edward Seto
The protein deacetylase SIRT1 (Sirtuin 1) regulates many cellular processes, including cell-cycle progression, DNA damage response, and metabolism. Although the centrosome is a key regulator of cell-cycle progression and genome stability, little is known concerning SIRT1 controlled centrosome-associated events. Here we report that the centrosome protein Plk2 is acetylated and undergoes deacetylation by SIRT1. Acetylation protects Plk2 from ubiquitination, and SIRT1-mediated deacetylation promotes ubiquitin-dependent degradation of Plk2...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517870/the-dachsous-fat-four-jointed-pathway-directs-the-uniform-axial-orientation-of-epithelial-cells-in-the-drosophila-abdomen
#8
Federica Mangione, Enrique Martín-Blanco
The achievement of the final form of an individual requires not only the control of cell size and differentiation but also integrative directional cues to instruct cell movements, positions, and orientations. In Drosophila, the adult epidermis of the abdomen is created de novo by histoblasts. As these expand and fuse, they uniformly orient along the anteroposterior axis. We found that the Dachsous/Fat/Four-jointed (Ds/Ft/Fj) pathway is key for their alignment. The refinement of the tissue-wide expression of the atypical cadherins Ds and Ft result in their polarization and directional adhesiveness...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517869/cooperative-transcription-factor-induction-mediates-hemogenic-reprogramming
#9
Andreia M Gomes, Ilia Kurochkin, Betty Chang, Michael Daniel, Kenneth Law, Namita Satija, Alexander Lachmann, Zichen Wang, Lino Ferreira, Avi Ma'ayan, Benjamin K Chen, Dmitri Papatsenko, Ihor R Lemischka, Kateri A Moore, Carlos-Filipe Pereira
During development, hematopoietic stem and progenitor cells (HSPCs) arise from specialized endothelial cells by a process termed endothelial-to-hematopoietic transition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we demonstrate that human fibroblasts can be reprogrammed into hemogenic cells by the same transcription factors. Induced cells display dynamic EHT transcriptional programs, generate hematopoietic progeny, possess HSPC cell surface phenotype, and repopulate immunodeficient mice for 3 months...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517868/polycomb-and-methylation-independent-roles-of-ezh2-as-a-transcription-activator
#10
Jung Kim, Yongik Lee, Xiaodong Lu, Bing Song, Ka-Wing Fong, Qi Cao, Jonathan D Licht, Jonathan C Zhao, Jindan Yu
Enhancer of Zeste 2 (EZH2) is the enzymatic subunit of Polycomb Repressive Complex 2 (PRC2), which catalyzes histone H3 lysine 27 trimethylation (H3K27me3) at target promoters for gene silencing. Here, we report that EZH2 activates androgen receptor (AR) gene transcription through direct occupancy at its promoter. Importantly, this activating role of EZH2 is independent of PRC2 and its methyltransferase activities. Genome-wide assays revealed extensive EZH2 occupancy at promoters marked by either H3K27ac or H3K27me3, leading to gene activation or repression, respectively...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517867/the-hdac-associated-sin3b-protein-represses-dream-complex-targets-and-cooperates-with-apc-c-to-promote-quiescence
#11
Anthony J Bainor, Siddharth Saini, Alexander Calderon, Raquel Casado-Polanco, Belén Giner-Ramirez, Claudia Moncada, David J Cantor, Amanda Ernlund, Larisa Litovchick, Gregory David
The mammalian DREAM complex is responsible for the transcriptional repression of hundreds of cell-cycle-related genes in quiescence. How the DREAM complex recruits chromatin-modifying entities to aid in its repression remains unknown. Using unbiased proteomics analysis, we have uncovered a robust association between the chromatin-associated Sin3B protein and the DREAM complex. We have determined that genetic inactivation of Sin3B results in the de-repression of DREAM target genes during quiescence but is insufficient to allow quiescent cells to resume proliferation...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517866/isre-reporter-mouse-reveals-high-basal-and-induced-type-i-ifn-responses-in-inflammatory-monocytes
#12
Melissa B Uccellini, Adolfo García-Sastre
Type I and type III interferons (IFNs) are critical for controlling viral infections. However, the precise dynamics of the IFN response have been difficult to define in vivo. Signaling through type I IFN receptors leads to interferon-stimulated response element (ISRE)-dependent gene expression and an antiviral state. As an alternative to tracking IFN, we used an ISRE-dependent reporter mouse to define the cell types, localization, and kinetics of IFN responding cells during influenza virus infection. We find that measurable IFN responses are largely limited to hematopoietic cells, which show a high sensitivity to IFN...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517865/b-cells-produce-the-tissue-protective-protein-relm%C3%AE-during-helminth-infection-which-inhibits-il-17-expression-and-limits-emphysema
#13
Fei Chen, Wenhui Wu, Lianhua Jin, Ariel Millman, Mark Palma, Darine W El-Naccache, Katherine E Lothstein, Chen Dong, Karen L Edelblum, William C Gause
Emphysema results in destruction of alveolar walls and enlargement of lung airspaces and has been shown to develop during helminth infections through IL-4R-independent mechanisms. We examined whether interleukin 17A (IL-17A) may instead modulate development of emphysematous pathology in mice infected with the helminth parasite Nippostrongylus brasiliensis. We found that transient elevations in IL-17A shortly after helminth infection triggered subsequent emphysema that destroyed alveolar structures. Furthermore, lung B cells, activated through IL-4R signaling, inhibited early onset of emphysematous pathology...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517864/cmv-primes-functional-alternative-signaling-in-adaptive-%C3%AE-g-nk-cells-but-is-subverted-by-lentivirus-infection-in-rhesus-macaques
#14
Spandan V Shah, Cordelia Manickam, Daniel R Ram, Kyle Kroll, Hannah Itell, Sallie R Permar, Dan H Barouch, Nichole R Klatt, R Keith Reeves
Despite burgeoning evidence demonstrating the adaptive properties of natural killer (NK) cells, mechanistic data explaining these phenomena are lacking. Following antibody sensitization, NK cells lacking the Fc receptor (FcR) signaling chain (Δg) acquire adaptive features, including robust proliferation, multifunctionality, rapid killing, and mobilization to sites of virus exposure. Using the rhesus macaque model, we demonstrate the systemic distribution of Δg NK cells expressing memory features, including downregulated Helios and Eomes...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517863/hdac3-regulates-the-transition-to-the-homeostatic-myelinating-schwann-cell-state
#15
Laura H Rosenberg, Anne-Laure Cattin, Xavier Fontana, Elizabeth Harford-Wright, Jemima J Burden, Ian J White, Jacob G Smith, Ilaria Napoli, Victor Quereda, Cristina Policarpi, Jamie Freeman, Robin Ketteler, Antonella Riccio, Alison C Lloyd
The formation of myelinating Schwann cells (mSCs) involves the remarkable biogenic process, which rapidly generates the myelin sheath. Once formed, the mSC transitions to a stable homeostatic state, with loss of this stability associated with neuropathies. The histone deacetylases histone deacetylase 1 (HDAC1) and HDAC2 are required for the myelination transcriptional program. Here, we show a distinct role for HDAC3, in that, while dispensable for the formation of mSCs, it is essential for the stability of the myelin sheath once formed-with loss resulting in progressive severe neuropathy in adulthood...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517862/inhibiting-stearoyl-coa-desaturase-ameliorates-%C3%AE-synuclein-cytotoxicity
#16
Benjamin M Vincent, Daniel F Tardiff, Jeff S Piotrowski, Rebecca Aron, Matthew C Lucas, Chee Yeun Chung, Helene Bacherman, YiQun Chen, Michelle Pires, Radha Subramaniam, Dimple B Doshi, Heather Sadlish, Waseem K Raja, Eric J Solís, Vikram Khurana, Bertrand Le Bourdonnec, Robert H Scannevin, Kenneth J Rhodes
The lack of disease-modifying treatments for neurodegenerative disease stems in part from our rudimentary understanding of disease mechanisms and the paucity of targets for therapeutic intervention. Here we used an integrated discovery paradigm to identify a new therapeutic target for diseases caused by α-synuclein (α-syn), a small lipid-binding protein that misfolds and aggregates in Parkinson's disease and other disorders. Using unbiased phenotypic screening, we identified a series of compounds that were cytoprotective against α-syn-mediated toxicity by inhibiting the highly conserved enzyme stearoyl-CoA desaturase (SCD)...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517861/a-primate-specific-isoform-of-plekhg6-regulates-neurogenesis-and-neuronal-migration
#17
Adam C O'Neill, Christina Kyrousi, Johannes Klaus, Richard J Leventer, Edwin P Kirk, Andrew Fry, Daniela T Pilz, Tim Morgan, Zandra A Jenkins, Micha Drukker, Samuel F Berkovic, Ingrid E Scheffer, Renzo Guerrini, David M Markie, Magdalena Götz, Silvia Cappello, Stephen P Robertson
The mammalian neocortex has undergone remarkable changes through evolution. A consequence of such rapid evolutionary events could be a trade-off that has rendered the brain susceptible to certain neurodevelopmental and neuropsychiatric conditions. We analyzed the exomes of 65 patients with the structural brain malformation periventricular nodular heterotopia (PH). De novo coding variants were observed in excess in genes defining a transcriptomic signature of basal radial glia, a cell type linked to brain evolution...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517860/long-term-memory-engram-cells-are-established-by-c-fos-creb-transcriptional-cycling
#18
Tomoyuki Miyashita, Emi Kikuchi, Junjiro Horiuchi, Minoru Saitoe
Training-dependent increases in c-fos have been used to identify engram cells encoding long-term memories (LTMs). However, the interaction between transcription factors required for LTM, including CREB and c-Fos, and activating kinases such as phosphorylated ERK (pERK) in the establishment of memory engrams has been unclear. Formation of LTM of an aversive olfactory association in flies requires repeated training trials with rest intervals between trainings. Here, we find that prolonged rest interval-dependent increases in pERK induce transcriptional cycling between c-Fos and CREB in a subset of KCs in the mushroom bodies, where olfactory associations are made and stored...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517859/supramammillary-nucleus-afferents-to-the-dentate-gyrus-co-release-glutamate-and-gaba-and-potentiate-granule-cell-output
#19
Yuki Hashimotodani, Fuyuki Karube, Yuchio Yanagawa, Fumino Fujiyama, Masanobu Kano
The supramammillary nucleus (SuM) of the hypothalamus projects to the dentate gyrus (DG) and the CA2 region of the hippocampus. Although the SuM-to-hippocampus circuits have been implicated in spatial and emotional memory formation, little is known about precise neural connections between the SuM and hippocampus. Here, we report that axons of SuM neurons make monosynaptic connections to granule cells (GCs) and GABAergic interneurons, but not to hilar mossy cells, in the DG and co-release glutamate and γ-aminobutyric acid (GABA) at these synapses...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30517858/single-cell-rna-seq-of-mouse-olfactory-bulb-reveals-cellular-heterogeneity-and-activity-dependent-molecular-census-of-adult-born-neurons
#20
Burak Tepe, Matthew C Hill, Brandon T Pekarek, Patrick J Hunt, Thomas J Martin, James F Martin, Benjamin R Arenkiel
Cellular heterogeneity within the mammalian brain poses a challenge toward understanding its complex functions. Within the olfactory bulb, odor information is processed by subtypes of inhibitory interneurons whose heterogeneity and functionality are influenced by ongoing adult neurogenesis. To investigate this cellular heterogeneity and better understand adult-born neuron development, we utilized single-cell RNA sequencing and computational modeling to reveal diverse and transcriptionally distinct neuronal and nonneuronal cell types...
December 4, 2018: Cell Reports
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