Exploring the transcriptome of ciliated cells using in silico dissection of human tissues

PLoS One. 2012;7(4):e35618. doi: 10.1371/journal.pone.0035618. Epub 2012 Apr 25.

Abstract

Cilia are cell organelles that play important roles in cell motility, sensory and developmental functions and are involved in a range of human diseases, known as ciliopathies. Here, we search for novel human genes related to cilia using a strategy that exploits the previously reported tendency of cell type-specific genes to be coexpressed in the transcriptome of complex tissues. Gene coexpression networks were constructed using the noise-resistant WGCNA algorithm in 12 publicly available microarray datasets from human tissues rich in motile cilia: airways, fallopian tubes and brain. A cilia-related coexpression module was detected in 10 out of the 12 datasets. A consensus analysis of this module's gene composition recapitulated 297 known and predicted 74 novel cilia-related genes. 82% of the novel candidates were supported by tissue-specificity expression data from GEO and/or proteomic data from the Human Protein Atlas. The novel findings included a set of genes (DCDC2, DYX1C1, KIAA0319) related to a neurological disease dyslexia suggesting their potential involvement in ciliary functions. Furthermore, we searched for differences in gene composition of the ciliary module between the tissues. A multidrug-and-toxin extrusion transporter MATE2 (SLC47A2) was found as a brain-specific central gene in the ciliary module. We confirm the localization of MATE2 in cilia by immunofluorescence staining using MDCK cells as a model. While MATE2 has previously gained attention as a pharmacologically relevant transporter, its potential relation to cilia is suggested for the first time. Taken together, our large-scale analysis of gene coexpression networks identifies novel genes related to human cell cilia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Cell Line
  • Cilia / genetics*
  • Cilia / metabolism
  • Cytoskeletal Proteins
  • Databases, Genetic
  • Dogs
  • Dyslexia / genetics*
  • Fallopian Tubes / cytology
  • Fallopian Tubes / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Microtubule-Associated Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity
  • Organic Cation Transport Proteins / genetics*
  • Proteomics / methods*
  • Respiratory System / cytology
  • Respiratory System / metabolism
  • Transcriptome

Substances

  • Cytoskeletal Proteins
  • DCDC2 protein, human
  • DNAAF4 protein, human
  • KIAA0319 protein, human
  • MATE2-K protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Organic Cation Transport Proteins