Subcellular Proteome Landscape of Human Embryonic Stem Cells Revealed Missing Membrane Proteins

M.M. Weldemariam, C.-L. Han, F. Shekari, R.B. Kitata, C.-Y. Chuang, W.-T. Hsu, H.-C. Kuo, W.-K. Choong, T.-Y. Sung, F.-C. He, M.C.M. Chung, G.H. Salekdeh, Y.-J. Chen

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17 Citations (Scopus)


Human embryonic stem cells (hESCs) have the capacity for self-renewal and multilineage differentiation, which are of clinical importance for regeneration medicine. Despite the significant progress of hESC study, the complete hESC proteome atlas, especially the surface protein composition, awaits delineation. According to the latest release of neXtProt database (January 17, 2018; 19658 PE1, 2, 3, and 4 human proteins), membrane proteins present the major category (1047; 48%) among all 2186 missing proteins (MPs). We conducted a deep subcellular proteomics analysis of hESCs to identify the nuclear, cytoplasmic, and membrane proteins in hESCs and to mine missing membrane proteins in the very early cell status. To our knowledge, our study achieved the largest data set with confident identification of 11970 unique proteins (1% false discovery rate at peptide, protein, and PSM levels), including the most-comprehensive description of 6138 annotated membrane proteins in hESCs. Following the HPP guideline, we identified 26 gold (neXtProt PE2, 3, and 4 MPs) and 87 silver (potential MP candidates with a single unique peptide detected) MPs, of which 69 were membrane proteins, and the expression of 21 gold MPs was further verified either by multiple reaction monitoring mass spectrometry or by matching synthetic peptides in the Peptide Atlas database. Functional analysis of the MPs revealed their potential roles in the pluripotency-related pathways and the lineage- and tissue-specific differentiation processes. Our proteome map of hESCs may provide a rich resource not only for the identification of MPs in the human proteome but also for the investigation on self-renewal and differentiation of hESC. Copyright © 2018 American Chemical Society.
Original languageEnglish
Pages (from-to)4138-4151
Number of pages14
JournalJournal of Proteome Research
Issue number12
Publication statusPublished - Dec 7 2018


  • human embryonic stem cells
  • membrane proteome
  • missing proteins
  • subcellular fractionation

ASJC Scopus subject areas

  • Biochemistry
  • General Chemistry


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