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J Proteome Res. 2018 Dec 7;17(12):4138-4151. doi: 10.1021/acs.jproteome.8b00407. Epub 2018 Sep 24.

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

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Institute of Chemistry, Academia Sinica , Taipei 115 , Taiwan.
Department of Chemistry , National Taiwan University , Taipei 112 , Taiwan.
Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy , Taipei Medical University , Taipei 110 , Taiwan.
Department of Molecular Systems Biology at Cell Science Research Center , Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran , Iran.
Genomics Research Center, Academia Sinica , Taiepei 115 , Taiwan.
Institutes of Biomedical Sciences , Fudan University , Shanghai 200433 , China.
State Key Laboratory of Proteomics , Beijing Proteome Research Center , Beijing , 102206 China.
Department of Biochemistry, Yong Loo Lin School of Medicine , NUS , 14 Science Drive 4 , singapore , 117543 Singpore.
Department of Molecular Sciences , Macquarie University , Sydney , New South Wales 2109 , Australia.
Department of Systems and Synthetic Biology , Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education, and Extension Organization , Karaj , Iran.


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; 19 658 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 11 970 unique proteins (1% false discovery rate at peptide, protein, and PSM levels), including the most-comprehensive description of 6 138 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.


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

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