A cell surfaceome map for immunophenotyping and sorting pluripotent stem cells

Mol Cell Proteomics. 2012 Aug;11(8):303-16. doi: 10.1074/mcp.M112.018135. Epub 2012 Apr 6.

Abstract

Induction of a pluripotent state in somatic cells through nuclear reprogramming has ushered in a new era of regenerative medicine. Heterogeneity and varied differentiation potentials among induced pluripotent stem cell (iPSC) lines are, however, complicating factors that limit their usefulness for disease modeling, drug discovery, and patient therapies. Thus, there is an urgent need to develop nonmutagenic rapid throughput methods capable of distinguishing among putative iPSC lines of variable quality. To address this issue, we have applied a highly specific chemoproteomic targeting strategy for de novo discovery of cell surface N-glycoproteins to increase the knowledge-base of surface exposed proteins and accessible epitopes of pluripotent stem cells. We report the identification of 500 cell surface proteins on four embryonic stem cell and iPSCs lines and demonstrate the biological significance of this resource on mouse fibroblasts containing an oct4-GFP expression cassette that is active in reprogrammed cells. These results together with immunophenotyping, cell sorting, and functional analyses demonstrate that these newly identified surface marker panels are useful for isolating iPSCs from heterogeneous reprogrammed cultures and for isolating functionally distinct stem cell subpopulations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Separation / methods*
  • Cells, Cultured
  • Cytokine Receptor gp130 / analysis
  • Embryo, Mammalian / cytology
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / transplantation
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Glycoproteins / analysis*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunophenotyping / methods*
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / transplantation
  • Mass Spectrometry
  • Membrane Proteins / analysis*
  • Mice
  • Mice, 129 Strain
  • Mice, Transgenic
  • Microscopy, Confocal
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Proteomics / methods*
  • Teratoma / metabolism
  • Teratoma / pathology

Substances

  • Glycoproteins
  • Membrane Proteins
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Cytokine Receptor gp130
  • Green Fluorescent Proteins