The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling

Abstract

Background

The gastrointestinal tract (GIT) is subdivided into different anatomical organs with many shared functions and characteristics, but also distinct differences. We have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to describe the gene and protein expression patterns that define the human GIT.

Methods

RNA sequencing data derived from stomach, duodenum, jejunum/ileum and colon specimens were compared to gene expression levels in 23 other normal human tissues analysed with the same method. Protein profiling based on immunohistochemistry and tissue microarrays was used to sub-localize the corresponding proteins with GIT-specific expression into sub-cellular compartments and cell types.

Results

Approximately 75 % of all human protein-coding genes were expressed in at least one of the GIT tissues. Only 51 genes showed enriched expression in either one of the GIT tissues and an additional 83 genes were enriched in two or more GIT tissues. The list of GIT-enriched genes with validated protein expression patterns included various well-known but also previously uncharacterised or poorly studied genes. For instance, the colon-enriched expression of NXPE family member 1 (NXPE1) was established, while NLR family, pyrin domain-containing 6 (NLRP6) expression was primarily found in the human small intestine.

Conclusions

We have applied a genome-wide analysis based on transcriptomics and antibody-based protein profiling to identify genes that are expressed in a specific manner within the human GIT. These genes and proteins constitute important starting points for an improved understanding of the normal function and the different states of disease associated with the GIT.

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Acknowledgments

Funding was provided by the Knut and Alice Wallenberg Foundation. Pathologists and staff at the Department of Clinical Pathology, Uppsala University Hospital are greatly acknowledged for providing the tissues used in the study, in particular, the authors would like to thank Simin Tahmasebpoor for excellent help with preparing frozen tissues for RNA extraction. The authors also wish to thank the staff of the Human Protein Atlas project in both Sweden and India for their efforts in generating the Human Protein Atlas.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The study was approved by the Uppsala Ethical Review Board (Reference 2011/473).

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Correspondence to Fredrik Pontén.

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Gremel, G., Wanders, A., Cedernaes, J. et al. The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling. J Gastroenterol 50, 46–57 (2015). https://doi.org/10.1007/s00535-014-0958-7

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Keywords

  • RNA expression
  • Immunohistochemistry
  • Gastrointestinal tract