A Global View of Protein Expression in Human Cells, Tissues, and Organs

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2009 Dec 24

PMID 20029370

Citations 85

Authors

Fredrik Ponten

Marcus Gry

Linn Fagerberg

Emma Lundberg

Anna Asplund

Lisa Berglund

Per Oksvold

Erik Bjorling

Sophia Hober

Caroline Kampf

Sanjay Navani

Peter Nilsson

Jenny Ottosson

Anja Persson

Henrik Wernerus

Kenneth Wester

Mathias Uhlen

Affiliations

Soon will be listed here.

Abstract

Defining the protein profiles of tissues and organs is critical to understanding the unique characteristics of the various cell types in the human body. In this study, we report on an anatomically comprehensive analysis of 4842 protein profiles in 48 human tissues and 45 human cell lines. A detailed analysis of over 2 million manually annotated, high-resolution, immunohistochemistry-based images showed a high fraction (>65%) of expressed proteins in most cells and tissues, with very few proteins (<2%) detected in any single cell type. Similarly, confocal microscopy in three human cell lines detected expression of more than 70% of the analyzed proteins. Despite this ubiquitous expression, hierarchical clustering analysis, based on global protein expression patterns, shows that the analyzed cells can be still subdivided into groups according to the current concepts of histology and cellular differentiation. This study suggests that tissue specificity is achieved by precise regulation of protein levels in space and time, and that different tissues in the body acquire their unique characteristics by controlling not which proteins are expressed but how much of each is produced.

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References

Larsson C, Koch J, Nygren A, Janssen G, Raap A, Landegren U . In situ genotyping individual DNA molecules by target-primed rolling-circle amplification of padlock probes. Nat Methods. 2005; 1(3):227-32. DOI: 10.1038/nmeth723. View

Tress M, Martelli P, Frankish A, Reeves G, Wesselink J, Yeats C . The implications of alternative splicing in the ENCODE protein complement. Proc Natl Acad Sci U S A. 2007; 104(13):5495-500. PMC: 1838448. DOI: 10.1073/pnas.0700800104. View

Berglund L, Bjorling E, Oksvold P, Fagerberg L, Asplund A, Szigyarto C . A genecentric Human Protein Atlas for expression profiles based on antibodies. Mol Cell Proteomics. 2008; 7(10):2019-27. DOI: 10.1074/mcp.R800013-MCP200. View

Saito-Hisaminato A, Katagiri T, Kakiuchi S, Nakamura T, Tsunoda T, Nakamura Y . Genome-wide profiling of gene expression in 29 normal human tissues with a cDNA microarray. DNA Res. 2002; 9(2):35-45. DOI: 10.1093/dnares/9.2.35. View

Bjorling E, Lindskog C, Oksvold P, Linne J, Kampf C, Hober S . A web-based tool for in silico biomarker discovery based on tissue-specific protein profiles in normal and cancer tissues. Mol Cell Proteomics. 2007; 7(5):825-44. DOI: 10.1074/mcp.M700411-MCP200. View

Lundberg E, Gry M, Oksvold P, Kononen J, Andersson-Svahn H, Ponten F . The correlation between cellular size and protein expression levels--normalization for global protein profiling. J Proteomics. 2008; 71(4):448-60. DOI: 10.1016/j.jprot.2008.06.014. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N . Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1998; 4(5):307-13. DOI: 10.1093/dnares/4.5.307. View

Clamp M, Fry B, Kamal M, Xie X, Cuff J, Lin M . Distinguishing protein-coding and noncoding genes in the human genome. Proc Natl Acad Sci U S A. 2007; 104(49):19428-33. PMC: 2148306. DOI: 10.1073/pnas.0709013104. View

10.

Yen H, Xu Q, Chou D, Zhao Z, Elledge S . Global protein stability profiling in mammalian cells. Science. 2008; 322(5903):918-23. DOI: 10.1126/science.1160489. View

11.

Golub T, Slonim D, Tamayo P, Huard C, Gaasenbeek M, Mesirov J . Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999; 286(5439):531-7. DOI: 10.1126/science.286.5439.531. View

12.

Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Bjorling E . Toward a confocal subcellular atlas of the human proteome. Mol Cell Proteomics. 2007; 7(3):499-508. DOI: 10.1074/mcp.M700325-MCP200. View

13.

Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M . Antisense transcription in the mammalian transcriptome. Science. 2005; 309(5740):1564-6. DOI: 10.1126/science.1112009. View

14.

Taylor C, Levenson R . Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment II. Histopathology. 2006; 49(4):411-24. DOI: 10.1111/j.1365-2559.2006.02513.x. View

15.

Sultan M, Schulz M, Richard H, Magen A, Klingenhoff A, Scherf M . A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science. 2008; 321(5891):956-60. DOI: 10.1126/science.1160342. View

16.

Birney E, Stamatoyannopoulos J, Dutta A, Guigo R, Gingeras T, Margulies E . Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007; 447(7146):799-816. PMC: 2212820. DOI: 10.1038/nature05874. View

17.

Mann M, Kelleher N . Precision proteomics: the case for high resolution and high mass accuracy. Proc Natl Acad Sci U S A. 2008; 105(47):18132-8. PMC: 2587563. DOI: 10.1073/pnas.0800788105. View

18.

Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S . Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998; 4(7):844-7. DOI: 10.1038/nm0798-844. View

19.

Kislinger T, Cox B, Kannan A, Chung C, Hu P, Ignatchenko A . Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling. Cell. 2006; 125(1):173-86. DOI: 10.1016/j.cell.2006.01.044. View

20.

Stromberg S, Bjorklund M, Asplund C, Skollermo A, Persson A, Wester K . A high-throughput strategy for protein profiling in cell microarrays using automated image analysis. Proteomics. 2007; 7(13):2142-50. DOI: 10.1002/pmic.200700199. View