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    Nature communications. 2021 Nov 12. doi: 10.1038/s41467-021-26879-4. pii: 10.1038/s41467-021-26879-4
    An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation.
    Sabatier P1,  Beusch CM2,  Saei AA3,  Aoun M4,  Moruzzi N5,  Coelho A6,  Leijten N7,  Nordenskjöld M8,  Micke P9,  Maltseva D10,  Tonevitsky AG11,  Millischer V12,  Carlos Villaescusa J13,  Kadekar S14,  Gaetani M15,  Altynbekova K16,  Kel A17,  Berggren PO18,  Simonson O19,  Grinnemo KH20,  Holmdahl R21,  Rodin S22,  Zubarev RA23
    Author information
    1Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
    2Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
    3Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
    4Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
    5The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, 17176, Sweden.
    6Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
    7Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, Utrecht, 3584 CH, The Netherlands.
    8Center for Molecular Medicine, Karolinska University Hospital, Stockholm, 171 76, Sweden.
    9Immunology, Genetics and Pathology, Rudbecklaboratoriet, Uppsala University, Uppsala, 751 85, Sweden.
    10Faculty of biology and biotechnology, National Research University Higher School of Economics, Myasnitskaya Street, 13/4, Moscow, 117997, Russia.
    11Faculty of biology and biotechnology, National Research University Higher School of Economics, Myasnitskaya Street, 13/4, Moscow, 117997, Russia.
    12Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, 17177, Sweden.
    13Neurogenetic Unit, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Stockholm, 171 76, Sweden.
    14Department of Surgical Sciences, Uppsala University, Uppsala, 752 37, Sweden.
    15Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
    16geneXplain GmbH, Am Exer 19B, 38302, Wolfenbuettel, Germany.
    17geneXplain GmbH, Am Exer 19B, 38302, Wolfenbuettel, Germany.
    18The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, 17176, Sweden.
    19Department of Surgical Sciences, Uppsala University, Uppsala, 752 37, Sweden.
    20Department of Surgical Sciences, Uppsala University, Uppsala, 752 37, Sweden.
    21Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
    22Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden. sergey.rodin@surgsci.uu.se.
    23Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden. roman.zubarev@ki.se.
    Abstract

    Detailed characterization of cell type transitions is essential for cell biology in general and particularly for the development of stem cell-based therapies in regenerative medicine. To systematically study such transitions, we introduce a method that simultaneously measures protein expression and thermal stability changes in cells and provide the web-based visualization tool ProteoTracker. We apply our method to study differences between human pluripotent stem cells and several cell types including their parental cell line and differentiated progeny. We detect alterations of protein properties in numerous cellular pathways and components including ribosome biogenesis and demonstrate that modulation of ribosome maturation through SBDS protein can be helpful for manipulating cell stemness in vitro. Using our integrative proteomics approach and the web-based tool, we uncover a molecular basis for the uncoupling of robust transcription from parsimonious translation in stem cells and propose a method for maintaining pluripotency in vitro.


    © 2021. The Author(s).

    Publikations ID: 34772928
    Quelle: öffnen
     
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