An epigenetic profile of early T-cell development from multipotent progenitors to committed T-cell descendants

Eur J Immunol. 2014 Apr;44(4):1181-93. doi: 10.1002/eji.201344022. Epub 2014 Feb 1.


Cellular differentiation of the T-cell branch of the immune system begins with the HSC, which undergoes a series of stages characterized by progressive restriction in multipotency and acquisition of specific lineage identity At the molecular level, the restriction of cell potential, commitment, and differentiation to a specific lineage is achieved through the coordinated control of gene expression and epigenetic mechanisms. Here, we analyzed and compared the gene expression profiles and the genome-wide histone modification marks H3K4me3 (H3 lysine 4 trimethylation) and H3K27me3 (H3 lysine 27 trimethylation) in (i) in vitro propagated HSCs, (ii) in vitro generated and propagated pro-T cells derived from these stem cells, and (iii) double-positive thymocytes derived from these pro-T cells after injection into Rag-deficient mice. The combined analyses of the different datasets in this unique experimental system highlighted the importance of both transcriptional and epigenetic repression in shaping the early phases of T-cell development.

Keywords: Development; Epigenetics; Genome-wide; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cells, Cultured
  • Cluster Analysis
  • Epigenesis, Genetic*
  • Epigenomics / methods*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Histones / metabolism
  • Lysine / metabolism
  • Methylation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Precursor Cells, T-Lymphoid / cytology
  • Precursor Cells, T-Lymphoid / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*


  • Histones
  • Lysine

Associated data

  • GEO/GSE47940
  • GEO/GSE47995