Subcellular proteome landscape of human embryonic stem cells revealed missing membrane proteins

Mehari Muuz Weldemariam, Chia-Li Han, Faezeh Shekari, Reta Birhanu Kitata, Ching-Yu Chuang, Wei-Ting Hsu, Hung-Chih Kuo, Wai-Kok Choong, Ting-Yi Sung, Fu-Chu He, Maxey Ching Ming Chung, Ghasem Hosseini Salekdeh, Yu-Ju Chen

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    15 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. All mass spectrometry data were deposited in ProteomeXchange via jPOST with identifier PXD009840.

    Original languageEnglish
    Pages (from-to)4138–4151
    Number of pages14
    JournalJournal of Proteome Research
    Issue number12
    Early online date11 Sep 2018
    Publication statusPublished - 7 Dec 2018


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


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