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 GrinnemoRikard Holmdahl, Sergey Rodin, Roman A Zubarev

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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.

Original languageEnglish
Article number6558
Number of pages16
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

© 2021. The Author(s).
Funding: Open access funding provided by Karolinska Institute.

Funding Information:
This study was supported by the Knut and Alice Wallenberg Foundation (grant KAW 2014.071 to R.A.Z. and 2015.0063 to R.A.Z. and R.H.); Uppsala County Council (to K.H.G.); RuFu (to K.H.G.); the Swedish Foundation for Strategic Research and the Swedish Government, StemTherapy (to K.H.G. and to S.R.); the HSE University Basic Research Program (to D.M.); the Russian Science Foundation project # 17-14-01338 (to A.G.T.); Novo Nordisk A/S, SRP Diabetes; the Swedish Research Council and the Family Erling-Persson Foundation. A.A.S. was supported by Swedish Research Council (grant 2020-00687) and the Swedish Society of Medicine (grant SLS-961262, 1086 Stiftelsen Albert Nilssons forskningsfond). R.A.Z. acknowledges the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2020-899).

Publisher Copyright:
© 2021, The Author(s).

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