SILAC labeling coupled to shotgun proteomics analysis of membrane proteins of liver stem/hepatocyte allows to candidate the inhibition of TGF-beta pathway as causal to differentiation

Claudia Montaldo, Carmine Mancone, Alice Conigliaro, Angela M. Cozzolino, Valeria de Nonno, Marco Tripodi

Research output: Contribution to journalArticle

Abstract

Background: Despite extensive research on hepatic cells precursors and their differentiated states, much remains to be learned about the mechanism underlying the self-renewal and differentiation.Results: We apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the resident liver stem cells (RLSCs) and their progeny spontaneously differentiated into epithelial/hepatocyte (RLSCdH). By means of nanoLC-MALDI-TOF/TOF approach, we identified and quantified 248 membrane proteins and 57 of them were found modulated during hepatocyte differentiation. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the most of membrane proteins found to be modulated are involved in cell-to-cell signaling/interaction pathways. Moreover, the upstream prediction analysis of proteins involved in cell-to-cell signaling and interaction unveiled that the activation of the mesenchymal to epithelial transition (MET), by the repression of TGFB1/Slug signaling, may be causal to hepatocyte differentiation.Conclusions: Taken together, this study increases the understanding of the underlying mechanisms modulating the complex biological processes of hepatic stem cell proliferation and differentiation.

Original languageEnglish
Article number15
JournalProteome Science
Volume12
Issue number1
DOIs
Publication statusPublished - Mar 15 2014

Keywords

  • Hepatocyte
  • Proteomics
  • SILAC
  • Stem cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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