Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Nat Commun. 2021 Nov 12;12(1):6558. doi: 10.1038/s41467-021-26879-4.
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.
细胞类型转变的详细特征对于细胞生物学是至关重要的，特别是对于再生医学中基于干细胞的治疗方法的发展。为了系统地研究这些转变，我们引入了一种方法，该方法可以同时测量细胞中的蛋白质表达和热稳定性变化，并提供基于网络的可视化工具 ProteoTracker。我们将我们的方法应用于研究人类多能干细胞与包括其亲本细胞系和分化后代在内的几种细胞类型之间的差异。我们检测到许多细胞途径和组成部分中的蛋白质性质的改变，包括核糖体生物发生，并证明通过 SBDS 蛋白调节核糖体成熟对于体外操纵细胞干性是有帮助的。使用我们的整合蛋白质组学方法和基于网络的工具，我们揭示了干细胞中强大的转录与简约的翻译之间解耦的分子基础，并提出了一种体外维持多能性的方法。
