The human liver-specific proteome defined by transcriptomics and antibody-based profiling
Artikel i vetenskaplig tidskrift, 2014

Human liver physiology and the genetic etiology of the liver diseases can potentially be elucidated through the identification of proteins with enriched expression in the liver. Here, we combined data from RNA sequencing (RNA-Seq) and antibody-based immunohistochemistry across all major human tissues to explore the human liver proteome with enriched expression, as well as the cell type-enriched expression in hepatocyte and bile duct cells. We identified in total 477 protein-coding genes with elevated expression in the liver: 179 genes have higher expression as compared to all the other analyzed tissues; 164 genes have elevated transcript levels in the liver shared with at least one other tissue type; and an additional 134 genes have a mild level of increased expression in the liver. We identified the precise localization of these proteins through antibody-based protein profiling and the subcellular localization of these proteins through immunofluorescent-based profiling. We also identified the biological processes and metabolic functions associated with these proteins, investigated their contribution in the occurrence of liver diseases, and identified potential targets for their treatment. Our study demonstrates the use of RNA-Seq and antibody-based immunohistochemistry for characterizing the human liver proteome, as well as the use of tissue-specific proteins in identification of novel drug targets and discovery of biomarkers.

HEPATOCELLULAR-CARCINOMA

DISEASES

HEPATITIS-C

Cell Biology

ATLAS

Biology

METABOLISM

RNA-SEQ

metabolism

SERUM

TISSUE-SPECIFIC GENES

EXPRESSION

RNA sequencing

DRUGS

Biochemistry & Molecular Biology

immunohistochemistry

Författare

C. Kampf

Uppsala universitet

Adil Mardinoglu

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

L. Fagerberg

Kungliga Tekniska Högskolan (KTH)

B. M. Hallstrom

Kungliga Tekniska Högskolan (KTH)

K. Edlund

Uppsala universitet

E. Lundberg

Kungliga Tekniska Högskolan (KTH)

F. Ponten

Uppsala universitet

Jens B Nielsen

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

M. Uhlen

Kungliga Tekniska Högskolan (KTH)

FASEB Journal

0892-6638 (ISSN) 1530-6860 (eISSN)

Vol. 28 2901-2914

Ämneskategorier

Biologiska vetenskaper

Infrastruktur

C3SE (Chalmers Centre for Computational Science and Engineering)

Styrkeområden

Livsvetenskaper och teknik

DOI

10.1096/fj.14-250555