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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 7 2018

Fingerprint

Proteome
Stem cells
Membrane Proteins
Proteins
Peptides
Atlases
Gold
Silver Proteins
Databases
Human Embryonic Stem Cells
Functional analysis
Nuclear Envelope
Nuclear Proteins
Silver
Proteomics
Medicine
Mass spectrometry
Regeneration
Mass Spectrometry
Cell Membrane

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Subcellular Proteome Landscape of Human Embryonic Stem Cells Revealed Missing Membrane Proteins. / Weldemariam, M.M.; Han, C.-L.; Shekari, F.; Kitata, R.B.; Chuang, C.-Y.; Hsu, W.-T.; Kuo, H.-C.; Choong, W.-K.; Sung, T.-Y.; He, F.-C.; Chung, M.C.M.; Salekdeh, G.H.; Chen, Y.-J.

In: Journal of Proteome Research, Vol. 17, No. 12, 07.12.2018, p. 4138-4151.

Research output: Contribution to journalArticle

Weldemariam, MM, Han, C-L, Shekari, F, Kitata, RB, Chuang, C-Y, Hsu, W-T, Kuo, H-C, Choong, W-K, Sung, T-Y, He, F-C, Chung, MCM, Salekdeh, GH & Chen, Y-J 2018, 'Subcellular Proteome Landscape of Human Embryonic Stem Cells Revealed Missing Membrane Proteins', Journal of Proteome Research, vol. 17, no. 12, pp. 4138-4151. https://doi.org/10.1021/acs.jproteome.8b00407
Weldemariam, M.M. ; Han, C.-L. ; Shekari, F. ; Kitata, R.B. ; Chuang, C.-Y. ; Hsu, W.-T. ; Kuo, H.-C. ; Choong, W.-K. ; Sung, T.-Y. ; He, F.-C. ; Chung, M.C.M. ; Salekdeh, G.H. ; Chen, Y.-J. / Subcellular Proteome Landscape of Human Embryonic Stem Cells Revealed Missing Membrane Proteins. In: Journal of Proteome Research. 2018 ; Vol. 17, No. 12. pp. 4138-4151.
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title = "Subcellular Proteome Landscape of Human Embryonic Stem Cells Revealed Missing Membrane Proteins",
abstract = "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 {\circledC} 2018 American Chemical Society.",
keywords = "human embryonic stem cells, membrane proteome, missing proteins, subcellular fractionation",
author = "M.M. Weldemariam and C.-L. Han and F. Shekari and R.B. Kitata and C.-Y. Chuang and W.-T. Hsu and H.-C. Kuo and W.-K. Choong and T.-Y. Sung and F.-C. He and M.C.M. Chung and G.H. Salekdeh and Y.-J. Chen",
note = "Export Date: 25 October 2018 Article in Press CODEN: JPROB Correspondence Address: Han, C.-L.; Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical UniversityTaiwan; email: was@tmu.edu.tw References: Rubin, L.L., Haston, K.M., Stem cell biology and drug discovery (2011) BMC Biol., 9, p. 42; Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., Yamanaka, S., Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors (2007) Cell, 131, pp. 861-872; Lu, T.-Y., Lu, R.-M., Liao, M.-Y., Yu, J., Chung, C.-H., Kao, C.-F., Wu, H.-C., Epithelial Cell Adhesion Molecule Regulation Is Associated with the Maintenance of the Undifferentiated Phenotype of Human Embryonic Stem Cells (2010) J. Biol. Chem., 285, pp. 8719-8732; Hu, Q., Rosenfeld, M.G., Epigenetic regulation of human embryonic stem cells (2012) Front. Genet., 3, p. 238; Ronquist, S.A.-O., Patterson, G., Muir, L.A., Lindsly, S., Chen, H., Brown, M., Wicha, M.S., Rajapakse, I., Algorithm for cellular reprogramming (2017) Proc. Natl. Acad. Sci. U. S. A., 114 (45), pp. 11832-11837; Ding, V.M.Y., Ling, L., Natarajan, S., Yap, M.G.S., Cool, S.M., Choo, A.B.H., FGF-2 modulates Wnt signaling in undifferentiated hESC and iPS cells through activated PI3-K/GSK3β signaling (2010) J. Cell. Physiol., 225, pp. 417-428; Bray, S.J., Notch signalling: A simple pathway becomes complex (2006) Nat. Rev. Mol. Cell Biol., 7, p. 11; Munz, M., Baeuerle, P.A., Gires, O., The Emerging Role of EpCAM in Cancer and Stem Cell Signaling (2009) Cancer Res., 69, pp. 5627-5629; Prokhorova, T.A., Rigbolt, K.T.G., Johansen, P.T., Henningsen, J., Kratchmarova, I., Kassem, M., Blagoev, B., Stable Isotope Labeling by Amino Acids in Cell Culture(SILAC) and Quantitative Comparison of the Membrane Proteomes of Self-renewing and Differentiating Human Embryonic Stem Cells (2009) Mol. Cell. Proteomics, 8, pp. 959-970; Omenn, G.S., Lane, L., Lundberg, E.K., Overall, C.M., Deutsch, E.W., Progress on the HUPO Draft Human Proteome: 2017 Metrics of the Human Proteome Project (2017) J. Proteome Res., 16 (12), pp. 4281-4287; Meyfour, A., Pahlavan, S., Sobhanian, H., Salekdeh, G.H., 17th Chromosome-Centric Human Proteome Project Symposium in Tehran (2018) Proteomics, 18, p. 1800012; Baker, M.S., Ahn, S.B., Mohamedali, A., Islam, M.T., Cantor, D., Verhaert, P.D., Fanayan, S., Ranganathan, S., Accelerating the search for the missing proteins in the human proteome (2017) Nat. Commun., 8, p. 14271; Paik, Y.-K., Overall, C.M., Deutsch, E.W., Van Eyk, J.E., Omenn, G.S., Progress and Future Direction of Chromosome-Centric Human Proteome Project (2017) J. Proteome Res., 16, pp. 4253-4258; Chen, Y., Li, Y., Zhong, J., Zhang, J., Chen, Z., Yang, L., Cao, X., Wang, T., Identification of Missing Proteins Defined by Chromosome-Centric Proteome Project in the Cytoplasmic Detergent-Insoluble Proteins (2015) J. 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year = "2018",
month = "12",
day = "7",
doi = "10.1021/acs.jproteome.8b00407",
language = "English",
volume = "17",
pages = "4138--4151",
journal = "Journal of Proteome Research",
issn = "1535-3893",
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TY - JOUR

T1 - Subcellular Proteome Landscape of Human Embryonic Stem Cells Revealed Missing Membrane Proteins

AU - Weldemariam, M.M.

AU - Han, C.-L.

AU - Shekari, F.

AU - Kitata, R.B.

AU - Chuang, C.-Y.

AU - Hsu, W.-T.

AU - Kuo, H.-C.

AU - Choong, W.-K.

AU - Sung, T.-Y.

AU - He, F.-C.

AU - Chung, M.C.M.

AU - Salekdeh, G.H.

AU - Chen, Y.-J.

N1 - Export Date: 25 October 2018 Article in Press CODEN: JPROB Correspondence Address: Han, C.-L.; Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical UniversityTaiwan; email: was@tmu.edu.tw References: Rubin, L.L., Haston, K.M., Stem cell biology and drug discovery (2011) BMC Biol., 9, p. 42; Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., Yamanaka, S., Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors (2007) Cell, 131, pp. 861-872; Lu, T.-Y., Lu, R.-M., Liao, M.-Y., Yu, J., Chung, C.-H., Kao, C.-F., Wu, H.-C., Epithelial Cell Adhesion Molecule Regulation Is Associated with the Maintenance of the Undifferentiated Phenotype of Human Embryonic Stem Cells (2010) J. Biol. Chem., 285, pp. 8719-8732; Hu, Q., Rosenfeld, M.G., Epigenetic regulation of human embryonic stem cells (2012) Front. Genet., 3, p. 238; Ronquist, S.A.-O., Patterson, G., Muir, L.A., Lindsly, S., Chen, H., Brown, M., Wicha, M.S., Rajapakse, I., Algorithm for cellular reprogramming (2017) Proc. Natl. Acad. Sci. U. S. A., 114 (45), pp. 11832-11837; Ding, V.M.Y., Ling, L., Natarajan, S., Yap, M.G.S., Cool, S.M., Choo, A.B.H., FGF-2 modulates Wnt signaling in undifferentiated hESC and iPS cells through activated PI3-K/GSK3β signaling (2010) J. Cell. Physiol., 225, pp. 417-428; Bray, S.J., Notch signalling: A simple pathway becomes complex (2006) Nat. Rev. Mol. Cell Biol., 7, p. 11; Munz, M., Baeuerle, P.A., Gires, O., The Emerging Role of EpCAM in Cancer and Stem Cell Signaling (2009) Cancer Res., 69, pp. 5627-5629; Prokhorova, T.A., Rigbolt, K.T.G., Johansen, P.T., Henningsen, J., Kratchmarova, I., Kassem, M., Blagoev, B., Stable Isotope Labeling by Amino Acids in Cell Culture(SILAC) and Quantitative Comparison of the Membrane Proteomes of Self-renewing and Differentiating Human Embryonic Stem Cells (2009) Mol. Cell. Proteomics, 8, pp. 959-970; Omenn, G.S., Lane, L., Lundberg, E.K., Overall, C.M., Deutsch, E.W., Progress on the HUPO Draft Human Proteome: 2017 Metrics of the Human Proteome Project (2017) J. Proteome Res., 16 (12), pp. 4281-4287; Meyfour, A., Pahlavan, S., Sobhanian, H., Salekdeh, G.H., 17th Chromosome-Centric Human Proteome Project Symposium in Tehran (2018) Proteomics, 18, p. 1800012; Baker, M.S., Ahn, S.B., Mohamedali, A., Islam, M.T., Cantor, D., Verhaert, P.D., Fanayan, S., Ranganathan, S., Accelerating the search for the missing proteins in the human proteome (2017) Nat. Commun., 8, p. 14271; Paik, Y.-K., Overall, C.M., Deutsch, E.W., Van Eyk, J.E., Omenn, G.S., Progress and Future Direction of Chromosome-Centric Human Proteome Project (2017) J. Proteome Res., 16, pp. 4253-4258; Chen, Y., Li, Y., Zhong, J., Zhang, J., Chen, Z., Yang, L., Cao, X., Wang, T., Identification of Missing Proteins Defined by Chromosome-Centric Proteome Project in the Cytoplasmic Detergent-Insoluble Proteins (2015) J. 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PY - 2018/12/7

Y1 - 2018/12/7

N2 - 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.

AB - 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.

KW - human embryonic stem cells

KW - membrane proteome

KW - missing proteins

KW - subcellular fractionation

UR - http://www.scopus.com/inward/record.url?scp=85054140584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054140584&partnerID=8YFLogxK

U2 - 10.1021/acs.jproteome.8b00407

DO - 10.1021/acs.jproteome.8b00407

M3 - Article

VL - 17

SP - 4138

EP - 4151

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 12

ER -