Large-scale mapping of mammalian transcriptomes identifies conserved genes associated with different cell states

Nucleic Acids Res. 2017 Feb 28;45(4):1657-1672. doi: 10.1093/nar/gkw1256.


Distinguishing cell states based only on gene expression data remains a challenging task. This is true even for analyses within a species. In cross-species comparisons, the results obtained by different groups have varied widely. Here, we integrate RNA-seq data from more than 40 cell and tissue types of four mammalian species to identify sets of associated genes as indicators for specific cell states in each species. We employ a statistical method, TROM, to identify both protein-coding and non-coding indicators. Next, we map the cell states within each species and also between species using these indicator genes. We recapitulate known phenotypic similarity between related cell and tissue types and reveal molecular basis for their similarity. We also report novel associations between several tissues and cell types with functional support. Moreover, our identified conserved associated genes are found to be a good resource for studying cell differentiation and reprogramming. Lastly, long non-coding RNAs can serve well as associated genes to indicate cell states. We further infer the biological functions of those non-coding associated genes based on their co-expressed protein-coding genes. This study demonstrates that combining statistical modeling with public RNA-seq data can be powerful for improving our understanding of cell identity control.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Cluster Analysis
  • Computational Biology / methods
  • Contig Mapping*
  • Evolution, Molecular*
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Gene Expression Regulation, Developmental
  • Gene Ontology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mammals / genetics*
  • Mice
  • Molecular Sequence Annotation
  • Multigene Family
  • Organ Specificity
  • Transcriptome*