Nature Cell Biology contents: June 2013 Volume 15 Number 6, pp 545 - 712

Advertisement Small Reactor – Big Results With CELLSTAR® CELLreactor™ Innovative: 50 ml filter tube for suspension cultures Safe: USP VI-certified 0.2 µm PTFE-coated capillary membrane Fast: Facilitates parallel experiments Simple: Cultivation and harvest in one tube Easy: Mixing by standard equipment More: http://www.gbo.com/bioscience TABLE OF CONTENTS June 2013 Volume 15, Issue 6 Turning Points Reviews News and Views Research Highlights Articles Letters Resource Erratum Advertisement See what nature is hiding BD Horizon™ Brilliant Violet™ polymer conjugates are brighter than traditional dyes and can help identify cell populations with lower receptor density than previously possible. Learn how to resolve rare and dim cell populations with our expanded set of tools and information and request a free sample at bdbiosciences.com/go/brilliant. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement CNIO, Nature, Nature Cell Biology and Nature Reviews Cancer present: CNIO Cancer Symposium: Frontiers in Tumor Heterogeneity and Plasticity October 27-30, 2013 Madrid, Spain Click here for more information or to register for this conference today!   Turning Points Top Translating experience: Thinking outside the box   p545 Tony Hunter doi:10.1038/ncb2771 Reviews Top Control of metastatic progression by microRNA regulatory networks   pp546 - 554 Nora Pencheva and Sohail F. Tavazoie doi:10.1038/ncb2769 Pencheva and Tavazoie discuss the recent advances in understanding how microRNAs control metastatic progression in cancer. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output   pp555 - 564 Christian C. Dibble and Brendan D. Manning doi:10.1038/ncb2763 The metabolic activity of a cell or organism must be regulated by nutrient availability. Dibble and Manning discuss how the activity of the mTORC1 complex, a master regulator of metabolism, is able to respond to the nutrient environment. News and Views Top Preventing lysosomal fat indigestion   pp565 - 567 Ana Maria Cuervo doi:10.1038/ncb2778 Autophagy contributes to lipid catabolism through direct mobilization and breakdown of cellular lipid stores. Two recent studies reveal the regulatory mechanisms activated by cells during starvation to ensure that the cellular compartments involved in autophagic lipid catabolism are ready to receive, process and use these lipids. The regulators represent attractive therapeutic targets to help fight lipid-excess-associated diseases. See also: Article by Settembre et al. | Article by O’Rourke & Ruvkun White to brite adipocyte transition and back again   pp568 - 569 Youn-Kyoung Lee and Chad A. Cowan doi:10.1038/ncb2776 Identification and characterization of a third type of adipocyte known as brite (brown-in-white) adipocytes has drawn considerable attention, as these cells are thought to regulate energy expenditure and may help combat obesity. Remarkably, white adipocytes can adopt the characteristics of brite adipocytes following cold stimulation, and this process is reversible in vivo. See also: Article by Rosenwald et al. YAP forces fibroblasts to feel the tension   pp570 - 572 Ori Maller, Christopher C. DuFort and Valerie M. Weaver doi:10.1038/ncb2777 Cancer-associated fibroblasts (CAFs) may contribute to tissue tension and cancer progression by increasing extracellular matrix (ECM) deposition and remodelling. However, how CAFs become activated and their roles in tumour mechanics have remained unclear. YAP is now identified as a tension-stimulated CAF activator that promotes malignancy through a mechanically reinforced feed-forward loop. See also: Article by Calvo et al. The quest for myelin in the adult brain   pp572 - 575 Emanuela Zuccaro and Paola Arlotta doi:10.1038/ncb2750 Although myelination largely occurs during early postnatal life, myelinating oligodendrocytes are still generated in the adult brain. Myelin turnover in the adult is necessary for proper neuronal function and is gravely compromised in myelin disorders. The lineage relationship between adult neural stem cells and adult-born oligodendrocytes has been clarified, highlighting molecular pathways that could potentially be targeted to favour de novo myelination in pathological situations. See also: Article by Rafalski et al. | Article by Ortega et al. Job-splitting among integrins   pp575 - 577 Ronen Zaidel-Bar doi:10.1038/ncb2770 How different integrin receptors for the same extracellular ligand transduce distinct cellular responses is unclear. The characterization of the class-specific adhesomes of β1 and αV integrins now shows that whereas αV integrins promote unbranched actin polymerization, β1 integrins induce myosin-II-dependent contractility, and both integrin subtypes synergistically mediate rigidity sensing. See also: Article by Schiller et al. Cell Biology JOBS of the week Postdoctoral Fellow in bioinformatics and stem cell biology The University of Texas Postdoctoral fellow in cancer biology and cell signaling Bioinformatics Institute, ASTAR, Singapore 3 PhD student positions available for Bioinformaticians at CNIC Spanish National Cardiovascular Research Center (CNIC) PhD student Ghent University - VIB Cytokine Receptor Lab Post Doctoral Fellow Aaron Diamond AIDS Research Center More Science jobs from Cell Biology EVENT Computational Cell Biology: The interplay 07.23.13 New York, US More science events from Research Highlights Top Death by mitochondrial Rb | No need for centromere-localized Aurora B | The mitochondrial Parkin receptor identified | p53 extends to the microenvironment Advertisement Introducing the S3™ Cell Sorter from Bio-Rad. This state-of-the-art benchtop solution features automated setup and costs up to 50% less than traditional systems. Watch the video to find out how the S3 can make a difference in your lab.   Articles Top A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages   pp579 - 590 Aliaksandra Radzisheuskaya, Gloryn Le Bin Chia, Rodrigo L. dos Santos, Thorold W. Theunissen, L. Filipe C. Castro, Jennifer Nichols and José C. R. Silva doi:10.1038/ncb2742 Using embryonic stem cells (ESCs) expressing controlled levels of Oct4 (a master transcription factor for pluripotency and reprogramming), Silva and colleagues show that although ESC levels of Oct4 are needed for pluripotency entry, Oct4 levels can decrease once pluripotency is established, without affecting self-renewal. However, ESC levels of Oct4 are required for differentiation to all lineages, as cells with low levels of Oct4 during differentiation remain in a naïve pluripotent state. CEP162 is an axoneme-recognition protein promoting ciliary transition zone assembly at the cilia base   pp591 - 601 Won-Jing Wang, Hwee Goon Tay, Rajesh Soni, Geoffrey S. Perumal, Mary G. Goll, Frank P. Macaluso, John M. Asara, Jeffrey D. Amack and Meng-Fu Bryan Tsou doi:10.1038/ncb2739 Axonemal microtubules are crosslinked to the surrounding plasma membrane at the ciliary base, in the transition zone. Tsou and colleagues have identified a centriole distal-end protein, CEP162, which mediates the association of transition zone components to axonemal microtubules. Oligodendrogliogenic and neurogenic adult subependymal zone neural stem cells constitute distinct lineages and exhibit differential responsiveness to Wnt signalling   pp602 - 613 Felipe Ortega, Sergio Gascón, Giacomo Masserdotti, Aditi Deshpande, Christiane Simon, Judith Fischer, Leda Dimou, D. Chichung Lie, Timm Schroeder and Benedikt Berninger doi:10.1038/ncb2736 Adult mouse subependymal neural stem cells (aNSCs) give rise to neuronal and oligodendroglial progeny. Berninger and colleagues use continuous live imaging and single-cell tracking to demonstrate that single aNSCs isolated from the mouse brain generate exclusively either oligodendrocytes or neurons. They also show that Wnt activation stimulates oligodendrogenic progenitor proliferation without affecting neurogenic clones. See also: Article by Rafalski et al. | News and Views by Zuccaro & Arlotta Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain   pp614 - 624 Victoria A. Rafalski, Peggy P. Ho, Jamie O. Brett, Duygu Ucar, Jason C. Dugas, Elizabeth A. Pollina, Lionel M. L. Chow, Adiljan Ibrahim, Suzanne J. Baker, Ben A. Barres, Lawrence Steinman and Anne Brunet doi:10.1038/ncb2735 Oligodendrocytes produce myelin in the central nervous system and can regenerate in adults. Brunet and colleagues show that inactivation of SIRT1 deacetylase increases the proliferation of oligodendrocyte progenitors partly by shifting other neural stem cells to this fate. Using genome-wide approaches, they delineate PDGFRα as a critical target of SIRT1 in its negative effects on oligodendrocyte lineage. See also: Article by Ortega et al. | News and Views by Zuccaro & Arlotta β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments   pp625 - 636 Herbert B. Schiller, Michaela-Rosemarie Hermann, Julien Polleux, Timothée Vignaud, Sara Zanivan, Caroline C. Friedel, Zhiqi Sun, Aurelia Raducanu, Kay-E. Gottschalk, Manuel Théry, Matthias Mann and Reinhard Fässler doi:10.1038/ncb2747 Faessler and colleagues analyse the distinct properties of β1 and αv integrin subclasses, and provide insight into the different protein compositions, signalling activities and contributions to rigidity sensing of adhesion sites anchored by each integrin subtype. See also: News and Views by Zaidel-Bar Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts   pp637 - 646 Fernando Calvo, Nil Ege, Araceli Grande-Garcia, Steven Hooper, Robert P. Jenkins, Shahid I. Chaudhry, Kevin Harrington, Peter Williamson, Emad Moeendarbary, Guillaume Charras and Erik Sahai doi:10.1038/ncb2756 Sahai and colleagues report that YAP is required for the establishment and function of cancer-associated fibroblasts. They propose that matrix stiffening promotes Src-mediated activation of YAP in fibroblasts, which is necessary for the cancer-associated fibroblast phenotype and further promotes matrix stiffening in a positive feedback loop. See also: News and Views by Maller et al. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop   pp647 - 658 Carmine Settembre, Rossella De Cegli, Gelsomina Mansueto, Pradip K. Saha, Francesco Vetrini, Orane Visvikis, Tuong Huynh, Annamaria Carissimo, Donna Palmer, Tiemo Jürgen Klisch, Amanda C. Wollenberg, Diego Di Bernardo, Lawrence Chan, Javier E. Irazoqui and Andrea Ballabio doi:10.1038/ncb2718 Ballabio and colleagues report that the transcription factor TFEB, which has a known role in autophagy, is induced by starvation and promotes transcription of PGC1α and PPARα. Intriguingly, targeted expression of TFEB in the liver blocks the development of metabolic syndrome in mouse models of obesity. See also: News and Views by Cuervo | Article by O’Rourke & Ruvkun Bi-directional interconversion of brite and white adipocytes   pp659 - 667 Matthias Rosenwald, Aliki Perdikari, Thomas Rülicke and Christian Wolfrum doi:10.1038/ncb2740 Brown adipose cells contribute to body temperature maintenance by converting lipids and glucose into heat, and can be found in white adipose tissue. Wolfrum and colleagues find a population of cells in white adipose tissue that can adopt brown or white characteristics in response to cold. See also: News and Views by Lee and Cowan MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability   pp668 - 676 Eyleen J. O’Rourke and Gary Ruvkun doi:10.1038/ncb2741 During fasting, cellular lipophagy is activated and lipid stores are catabolized. O’Rourke and Ruvkun identify two metabolic transcriptional regulators, MXL-3 and HLH-30, which orchestrate the adaptive response to fasting by modulating the expression of lysosomal lipases and autophagy genes. In addition, they show that these regulators can influence C. elegans aging. See also: News and Views by Cuervo | Article by Settembre et al. The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis   pp677 - 687 Kun Zhang, Callie A. Corsa, Suzanne M. Ponik, Julie L. Prior, David Piwnica-Worms, Kevin W. Eliceiri, Patricia J. Keely and Gregory D. Longmore doi:10.1038/ncb2743 Longmore and colleagues show that in cancer cells that have undergone epithelial-to-mesenchymal transition (EMT), activation of the collagen I receptor DDR2 results in ERK2-dependent maintenance of the protein levels and activity of the EMT inducer SNAIL1, thus facilitating cancer cell invasion and metastasis. Letters Top Synergy between XMAP215 and EB1 increases microtubule growth rates to physiological levels   pp688 - 693 Marija Zanic, Per O. Widlund, Anthony A. Hyman and Jonathon Howard doi:10.1038/ncb2744 Howard and colleagues demonstrate that the XMAP215 and EB1 microtubule plus-end binding proteins synergistically promote microtubule growth in vitro, at rates comparable to those measured in cells. Effect of nuclear architecture on the efficiency of double-strand break repair   pp694 - 699 Neta Agmon, Batia Liefshitz, Christophe Zimmer, Emmanuelle Fabre and Martin Kupiec doi:10.1038/ncb2745 For double-strand breaks to be repaired by homologous recombination, the homologous template must be in the nuclear space. By elegant genetic manipulation of yeast chromosomes, Kupiec and colleagues show that nuclear organization influences repair efficiency. Resource Top Subtelomeric hotspots of aberrant 5-hydroxymethylcytosine-mediated epigenetic modifications during reprogramming to pluripotency   pp700 - 711 Tao Wang, Hao Wu, Yujing Li, Keith E. Szulwach, Li Lin, Xuekun Li, I-Ping Chen, Ian S. Goldlust, Stormy J. Chamberlain, Ann Dodd, He Gong, Gene Ananiev, Ji Woong Han, Young-sup Yoon, M. Katharine Rudd, Miao Yu, Chun-Xiao Song, Chuan He, Qiang Chang, Stephen T. Warren and Peng Jin doi:10.1038/ncb2748 Human embryonic stem cells contain 5-hydroxymethylcytosine (5hmC) generated by the TET enzyme. Jin and colleagues show that TET1 increases 5hmC levels during reprogramming to human inducible pluripotent stem cells, and although this change is critical for optimal epigenetic reprogramming, it does not compromise primed pluripotency. Erratum Top A global analysis of SNX27-retromer assembly and cargo specicity reveals a function in glucose and metal ion transport   p712 Florian Steinberg, Matthew Gallon, Mark Winfield, Elaine C. Thomas, Amanda J. Bell, Kate J. Heesom, Jeremy M. Tavaré and Peter J. Cullen doi:10.1038/ncb2780 Top Advertisement The Wellcome Trust and Nature Genetics present: The Genomics of Common Diseases 2013 September 7-10, 2013 Keble College, Oxford, UK Click here for more information or to register for this conference today!   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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