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An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation

Author

Listed:
  • Pierre Sabatier

    (Karolinska Institute)

  • Christian M. Beusch

    (Karolinska Institute)

  • Amir A. Saei

    (Karolinska Institute
    Harvard Medical School)

  • Mike Aoun

    (Karolinska Institute)

  • Noah Moruzzi

    (Karolinska Institute)

  • Ana Coelho

    (Karolinska Institute)

  • Niels Leijten

    (Utrecht University)

  • Magnus Nordenskjöld

    (Karolinska University Hospital
    Karolinska Institute
    Karolinska University Hospital)

  • Patrick Micke

    (Uppsala University)

  • Diana Maltseva

    (National Research University Higher School of Economics)

  • Alexander G. Tonevitsky

    (National Research University Higher School of Economics
    Scientific Research Center Bioclinicum)

  • Vincent Millischer

    (Karolinska Institute
    Karolinska University Hospital
    Medical University of Vienna)

  • J. Carlos Villaescusa

    (Karolinska University Hospital
    Stem Cell R&D—TRU, Novo Nordisk A/S)

  • Sandeep Kadekar

    (Uppsala University)

  • Massimiliano Gaetani

    (Karolinska Institute
    Karolinska Institutet
    Chemical Proteomics, Science for Life Laboratory (SciLifeLab))

  • Kamilya Altynbekova

    (geneXplain GmbH, Am Exer 19B)

  • Alexander Kel

    (geneXplain GmbH, Am Exer 19B)

  • Per-Olof Berggren

    (Karolinska Institute)

  • Oscar Simonson

    (Uppsala University
    Uppsala University Hospital)

  • Karl-Henrik Grinnemo

    (Uppsala University
    Uppsala University Hospital)

  • Rikard Holmdahl

    (Karolinska Institute)

  • Sergey Rodin

    (Karolinska Institute
    Uppsala University
    Uppsala University Hospital)

  • Roman A. Zubarev

    (Karolinska Institute
    I.M. Sechenov First Moscow State Medical University
    The National Medical Research Center for Endocrinology)

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.

Suggested Citation

  • Pierre Sabatier & Christian M. Beusch & Amir A. Saei & Mike Aoun & Noah Moruzzi & Ana Coelho & Niels Leijten & Magnus Nordenskjöld & Patrick Micke & Diana Maltseva & Alexander G. Tonevitsky & Vincent , 2021. "An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26879-4
    DOI: 10.1038/s41467-021-26879-4
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    References listed on IDEAS

    as
    1. Avni Baser & Maxim Skabkin & Susanne Kleber & Yonglong Dang & Gülce S. Gülcüler Balta & Georgios Kalamakis & Manuel Göpferich & Damian Carvajal Ibañez & Roman Schefzik & Alejandro Santos Lopez & Enric, 2019. "Onset of differentiation is post-transcriptionally controlled in adult neural stem cells," Nature, Nature, vol. 566(7742), pages 100-104, February.
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    3. Amir Ata Saei & Christian M. Beusch & Pierre Sabatier & Juan Astorga Wells & Hassan Gharibi & Zhaowei Meng & Alexey Chernobrovkin & Sergey Rodin & Katja Näreoja & Ann-Gerd Thorsell & Tobias Karlberg &, 2021. "System-wide identification and prioritization of enzyme substrates by thermal analysis," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Amir Ata Saei & Christian Michel Beusch & Alexey Chernobrovkin & Pierre Sabatier & Bo Zhang & Ülkü Güler Tokat & Eleni Stergiou & Massimiliano Gaetani & Ákos Végvári & Roman A. Zubarev, 2019. "ProTargetMiner as a proteome signature library of anticancer molecules for functional discovery," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    5. Ryohichi Sugimura & Deepak Kumar Jha & Areum Han & Clara Soria-Valles & Edroaldo Lummertz da Rocha & Yi-Fen Lu & Jeremy A. Goettel & Erik Serrao & R. Grant Rowe & Mohan Malleshaiah & Irene Wong & Patr, 2017. "Haematopoietic stem and progenitor cells from human pluripotent stem cells," Nature, Nature, vol. 545(7655), pages 432-438, May.
    6. Sabina Kanton & Michael James Boyle & Zhisong He & Malgorzata Santel & Anne Weigert & Fátima Sanchís-Calleja & Patricia Guijarro & Leila Sidow & Jonas Simon Fleck & Dingding Han & Zhengzong Qian & Mic, 2019. "Organoid single-cell genomic atlas uncovers human-specific features of brain development," Nature, Nature, vol. 574(7778), pages 418-422, October.
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