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

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 Millischer, J. Carlos Villaescusa, Sandeep Kadekar, Massimiliano Gaetani, Kamilya Altynbekova, Alexander Kel, Per-Olof Berggren, Oscar Simonson, Karl-Henrik Grinnemo, Rikard Holmdahl, Sergey Rodin () and Roman A. Zubarev ()
Additional contact information
Pierre Sabatier: Karolinska Institute
Christian M. Beusch: Karolinska Institute
Amir A. Saei: Karolinska Institute
Mike Aoun: Karolinska Institute
Noah Moruzzi: Karolinska Institute
Ana Coelho: Karolinska Institute
Niels Leijten: Utrecht University
Magnus Nordenskjöld: 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
Vincent Millischer: Karolinska Institute
J. Carlos Villaescusa: Karolinska University Hospital
Sandeep Kadekar: Uppsala University
Massimiliano Gaetani: Karolinska Institute
Kamilya Altynbekova: geneXplain GmbH, Am Exer 19B
Alexander Kel: geneXplain GmbH, Am Exer 19B
Per-Olof Berggren: Karolinska Institute
Oscar Simonson: Uppsala University
Karl-Henrik Grinnemo: Uppsala University
Rikard Holmdahl: Karolinska Institute
Sergey Rodin: Karolinska Institute
Roman A. Zubarev: Karolinska Institute

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26879-4

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