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  • Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β‐cell function
    Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β‐cell function
    1. Shiqi Jia*,1,,
    2. Andranik Ivanov2,,
    3. Dinko Blasevic1,
    4. Thomas Müller1,
    5. Bettina Purfürst3,
    6. Wei Sun46,
    7. Wei Chen4,
    8. Matthew N Poy5,
    9. Nikolaus Rajewsky2 and
    10. Carmen Birchmeier*,1
    1. 1Developmental Biology, Max‐Delbrück‐Center for Molecular Medicine, Berlin, Germany
    2. 2Systems Biology of Gene Regulatory Elements, Max‐Delbrück‐Center for Molecular Medicine, Berlin, Germany
    3. 3Electron Microscopy Platform, Max‐Delbrück‐Center for Molecular Medicine, Berlin, Germany
    4. 4Scientific Genomics Platform, Max‐Delbrück‐Center for Molecular Medicine, Berlin, Germany
    5. 5Molecular Mechanisms of Metabolic Disease, Max‐Delbrück‐Center for Molecular Medicine, Berlin, Germany
    6. 6Department of Medical Oncology, Jiangsu Provincial Hospital of TCM, Nanjing, China
    1. * Corresponding author. Tel: +49 30 9406 2403; Fax: +49 30 9406 3765; E‐mail: cbirch{at}mdc-berlin.de

      Corresponding author. Tel: +49 30 9406 3848; Fax: +49 30 9406 3765; E‐mail: jshiqi{at}mdc-berlin.de

    1. These authors contributed equally to this work

    The functional and molecular characterization of Insm1 reveals its crucial role in the maintenance of adult pancreatic β‐cell identity.

    Synopsis

    The functional and molecular characterization of Insm1 reveals its crucial role in the maintenance of adult pancreatic β‐cell identity.

    • Deletion of Insm1 in adult pancreatic β‐cells in mice translates into deficits of insulin secretion.

    • Insm1/Neurod1/Foxa2 co‐occupy regulatory sequences to maintain a mature gene expression profile in pancreatic β‐cells.

    • Corresponding human Insm1/Neurod1/Foxa2 binding regions show sequence variations that have been implicated in β‐cell dysfunction(s).

    • development
    • differentiation
    • Insm1
    • maturation
    • metabolisms
    • pancreatic beta cells
    • Received December 16, 2014.
    • Revision received February 26, 2015.
    • Accepted March 10, 2015.

    This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

    Shiqi Jia, Andranik Ivanov, Dinko Blasevic, Thomas Müller, Bettina Purfürst, Wei Sun, Wei Chen, Matthew N Poy, Nikolaus Rajewsky, Carmen Birchmeier
  • Blocking integrin inactivation as an anti‐angiogenic therapy
    Blocking integrin inactivation as an anti‐angiogenic therapy
    1. Pipsa Saharinen1 and
    2. Johanna Ivaska (joivaska{at}utu.fi) 2
    1. 1Wihuri Research Institute and Research Programs Unit, Translational Cancer Biology Program and Department of Virology, University of Helsinki, Helsinki, Finland
    2. 2Department of Food and Biochemistry, Turku Centre for Biotechnology University of Turku, Turku, Finland

    During angiogenesis, endothelial cell migration is coordinated by integrin‐mediated contact with the extra‐cellular matrix (ECM), coupled with receptor tyrosine kinase signalling to regulate dynamic cytoskeletal and plasma membrane reorganization. A recent paper by Vitorino et al (2015) defined a new MAP4K4–moesin–talin–β1‐integrin pathway that could be therapeutically exploited to suppress pathologic angiogenesis.

    See also: P Vitorino et al (March 2015)

    A recent study in Nature reports on the discovery of a MAP4K4‐dependent mechanism for integrin inactivation and endothelial cell migration. This leads the authors to pharmacological exploration for anti‐angiogenic therapies.

    Pipsa Saharinen, Johanna Ivaska
  • Plasmolipin—a new player in endocytosis and epithelial development
    Plasmolipin—a new player in endocytosis and epithelial development
    1. Armelle Le Guelte1 and
    2. Ian G Macara (ian.g.macara{at}Vanderbilt.Edu) 1
    1. 1Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Polarized vesicle sorting is essential not only for epithelial cell function but also for cell polarization and tissue morphogenesis. Endocytosis is a key determinant of the surface abundance of plasma membrane proteins and is highly regulated. In an important recent paper, Rodríguez‐Fraticelli et al (2015) identify a new player in apical endocytosis—a previously uncharacterized protein called Plasmolipin. They report not only its mechanism of action through binding to an epsin, but also highlight an essential role in regulating Notch signaling, which controls epithelial differentiation.

    See also: AE Rodríguez-Fraticelli et al (March 2015)

    Plasmolipin is a novel component of the apical endocytosis machinery that not only controls proper epithelial polarization, but is also involved in intestinal cell fate specification in zebrafish through the control of Notch signaling.

    Armelle Le Guelte, Ian G Macara
  • Reprogramming of cell fate: epigenetic memory and the erasure of memories past
    Reprogramming of cell fate: epigenetic memory and the erasure of memories past
    1. Buhe Nashun1,,
    2. Peter WS Hill1, and
    3. Petra Hajkova*,1
    1. 1Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, UK
    1. *Corresponding author. Tel: +44 20 83838264; E‐mail: petra.hajkova{at}csc.mrc.ac.uk
    1. These authors contributed equally to this work

    Petra Hajkova & colleagues feature the interplay of chromatin structure with cell fate determining transcription factors as therapeutic opportunity in the context of cellular reprogramming.

    • cell fate
    • chromatin
    • induced pluripotent stem cells
    • reprogramming
    • transcription factors
    • Received November 25, 2014.
    • Revision received February 26, 2015.
    • Accepted March 18, 2015.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Buhe Nashun, Peter WS Hill, Petra Hajkova
  • Cockayne syndrome group B protein regulates DNA double‐strand break repair and checkpoint activation
    Cockayne syndrome group B protein regulates DNA double‐strand break repair and checkpoint activation
    1. Nicole L Batenburg1,
    2. Elizabeth L Thompson2,
    3. Eric A Hendrickson2 and
    4. Xu‐Dong Zhu*,1
    1. 1Department of Biology, McMaster University, Hamilton, ON, Canada
    2. 2Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN, USA
    1. *Corresponding author. Tel: +1 905 525 9140 ext. 27737; Fax: +1 905 522 6066; E‐mail: zhuxu{at}mcmaster.ca

    Generation of human cells lacking the transcription‐coupled repair protein CSB reveals unexpected roles in DNA double‐strand break repair pathway choice and activation of ATM‐mediated DNA damage responses.

    Synopsis

    Loss of the Cockayne syndrome‐mutated CSB protein, best understood for its roles in transcription‐coupled nucleotide excision repair, leads to attenuation of DNA damage checkpoint responses and reveals a CSB role in DNA double‐strand break repair pathway choice.

    • CSB associates with sites of DNA double‐strand breaks (DSBs) in a transcription‐dependent manner.

    • CSB promotes BRCA1 recruitment to facilitate homologous recombination‐mediated DSB repair.

    • CSB suppresses the accumulation of 53BP1 and Rif1 in S/G2 cells, preventing non‐homologous end‐joining repair.

    • CSB is needed to maintain the full activation of ATM‐ and Chk2‐mediated DNA damage responses.

    • CSB
    • DNA damage checkpoint
    • DNA double‐strand break repair
    • Received September 11, 2014.
    • Revision received January 25, 2015.
    • Accepted March 11, 2015.
    Nicole L Batenburg, Elizabeth L Thompson, Eric A Hendrickson, Xu‐Dong Zhu
  • Telomerase abrogates aneuploidy‐induced telomere replication stress, senescence and cell depletion
    Telomerase abrogates aneuploidy‐induced telomere replication stress, senescence and cell depletion
    1. Jitendra K Meena1,
    2. Aurora Cerutti2,
    3. Christine Beichler3,
    4. Yohei Morita1,
    5. Christopher Bruhn1,
    6. Mukesh Kumar4,
    7. Johann M Kraus5,
    8. Michael R Speicher3,
    9. Zhao‐Qi Wang1,
    10. Hans A Kestler1,5,
    11. Fabrizio d'Adda di Fagagna2,6,
    12. Cagatay Günes*,1 and
    13. Karl Lenhard Rudolph*,1
    1. 1Leibniz Institute of Age Research, Fritz Lipmann Institute e.V., Jena, Germany
    2. 2IFOM Foundation—FIRC Institute of Molecular Oncology Foundation, Milan, Italy
    3. 3Institute of Human Genetics, Medical University of Graz, Graz, Austria
    4. 4Institute of Experimental Cancer Research, University of Ulm, Ulm, Germany
    5. 5Medical Systems Biology Unit, Ulm University, Ulm, Germany
    6. 6Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy
    1. * Corresponding author. Tel: +49 3641 656820; Fax: +49 3641 656351; E‐mail: cguenes{at}fli-leibniz.de

      Corresponding author. Tel: +49 3641 656350; Fax: +49 3641 656351; E‐mail: klrudolph{at}fli-leibniz.de

    This study reports on new regulators of aneuploidy‐induced replication stress and characterizes telomerase activity as sufficient to bypass aneuploidy‐induced replication stress at telomeres.

    Synopsis

    This study reports on new regulators of aneuploidy‐induced replication stress and characterizes telomerase activity as sufficient to bypass aneuploidy‐induced replication stress.

    • Aneuploidy induces telomere replication stress and premature senescence in primary human cells.

    • Telomerase rescues aneuploidy‐induced replication stress at telomeres and premature senescence.

    • Endogenous telomerase in stem cells is sufficient to abrogate aneuploidy‐induced replication stress.

    • Telomerase activity represents an aneuploidy survival mechanism in mammalian cells.

    • aneuploidy
    • replication stress
    • senescence
    • telomerase
    • telomere
    • Received September 16, 2014.
    • Revision received March 3, 2015.
    • Accepted March 4, 2015.
    Jitendra K Meena, Aurora Cerutti, Christine Beichler, Yohei Morita, Christopher Bruhn, Mukesh Kumar, Johann M Kraus, Michael R Speicher, Zhao‐Qi Wang, Hans A Kestler, Fabrizio d'Adda di Fagagna, Cagatay Günes, Karl Lenhard Rudolph
  • Switching roles: the functional plasticity of adult tissue stem cells
    Switching roles: the functional plasticity of adult tissue stem cells
    1. Agnieszka Wabik1 and
    2. Philip H Jones*,1,2
    1. 1MRC Cancer Unit, University of Cambridge Hutchison/MRC Research Centre Cambridge Biomedical Campus, Cambridge, UK
    2. 2Wellcome Trust Sanger Institute, Hinxton, UK
    1. *Corresponding author. Tel: +44 1223 763379; E‐mail: phj20{at}mrc-cu.cam.ac.uk

    This review compares the structural make‐up of distinct adult stem cell niches, describes their plasticity upon damage/during regeneration and alludes to modes of their physiological regulation.

    • differentiation
    • niche
    • regeneration
    • signal transduction
    • stem cells
    • Received October 23, 2014.
    • Revision received January 9, 2015.
    • Accepted February 11, 2015.
    Agnieszka Wabik, Philip H Jones