Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells

Immunity. 2009 Apr 17;30(4):493-507. doi: 10.1016/j.immuni.2009.01.014. Epub 2009 Apr 2.

Abstract

The mechanisms regulating lineage potential during early hematopoiesis were investigated. First, a cascade of lineage-affiliated gene expression signatures, primed in hematopoietic stem cells (HSCs) and differentially propagated in lineage-restricted progenitors, was identified. Lymphoid transcripts were primed as early as the HSC, together with myeloid and erythroid transcripts. Although this multilineage priming was resolved upon subsequent lineage restrictions, an unexpected cosegregation of lymphoid and myeloid gene expression and potential past a nominal myeloid restriction point was identified. Finally, we demonstrated that whereas the zinc finger DNA-binding factor Ikaros was required for induction of lymphoid lineage priming in the HSC, it was also necessary for repression of genetic programs compatible with self-renewal and multipotency downstream of the HSC. Taken together, our studies provide new insight into the priming and restriction of lineage potentials during early hematopoiesis and identify Ikaros as a key bivalent regulator of this process.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Lineage*
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Genome*
  • Hematopoiesis / immunology
  • Hematopoietic Stem Cells / immunology*
  • Ikaros Transcription Factor / metabolism*
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic

Substances

  • Zfpn1a1 protein, mouse
  • Ikaros Transcription Factor

Associated data

  • GEO/GSE15330