Cell-Surface Proteomics Identifies Differences in Signaling and Adhesion Protein Expression between Naive and Primed Human Pluripotent Stem Cells

Stem Cell Reports. 2020 May 12;14(5):972-988. doi: 10.1016/j.stemcr.2020.03.017. Epub 2020 Apr 16.

Abstract

Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes. The lack of detailed information about cell-surface protein expression in these two pluripotent cell types prevents an understanding of how the cells communicate and interact with their microenvironments. Here, we used plasma membrane profiling to directly measure cell-surface protein expression in naive and primed hPSC. This unbiased approach quantified over 1,700 plasma membrane proteins, including those involved in cell adhesion, signaling, and cell interactions. Notably, multiple cytokine receptors upstream of JAK-STAT signaling were more abundant in naive hPSC. In addition, functional experiments showed that FOLR1 and SUSD2 proteins are highly expressed at the cell surface in naive hPSC but are not required to establish human naive pluripotency. This study provides a comprehensive stem cell proteomic resource that uncovers differences in signaling pathway activity and has identified new markers to define human pluripotent states.

Keywords: JAK-STAT; cell state; cell-surface markers; embryonic; human; plasma membrane; pluripotent stem cell; proteomics; reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion*
  • Cell Line
  • Cell Membrane / metabolism*
  • Folate Receptor 1 / genetics
  • Folate Receptor 1 / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Proteome / genetics*
  • Proteome / metabolism
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Signal Transduction*

Substances

  • Cell Adhesion Molecules
  • FOLR1 protein, human
  • Folate Receptor 1
  • Membrane Glycoproteins
  • Proteome
  • Receptors, Cytokine
  • SUSD2 protein, human