Identification of transcriptional regulators in the mouse immune system

Nat Immunol. 2013 Jun;14(6):633-43. doi: 10.1038/ni.2587. Epub 2013 Apr 28.

Abstract

The differentiation of hematopoietic stem cells into cells of the immune system has been studied extensively in mammals, but the transcriptional circuitry that controls it is still only partially understood. Here, the Immunological Genome Project gene-expression profiles across mouse immune lineages allowed us to systematically analyze these circuits. To analyze this data set we developed Ontogenet, an algorithm for reconstructing lineage-specific regulation from gene-expression profiles across lineages. Using Ontogenet, we found differentiation stage-specific regulators of mouse hematopoiesis and identified many known hematopoietic regulators and 175 previously unknown candidate regulators, as well as their target genes and the cell types in which they act. Among the previously unknown regulators, we emphasize the role of ETV5 in the differentiation of γδ T cells. As the transcriptional programs of human and mouse cells are highly conserved, it is likely that many lessons learned from the mouse model apply to humans.

Publication types

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

MeSH terms

  • Algorithms*
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology*
  • Gene Regulatory Networks / immunology
  • Humans
  • Immune System / cytology
  • Immune System / metabolism*
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcription, Genetic / immunology*
  • Transcriptome / genetics
  • Transcriptome / immunology

Substances

  • DNA-Binding Proteins
  • Etv5 protein, mouse
  • Receptors, Antigen, T-Cell, gamma-delta
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors

Associated data

  • GEO/GSE15907