Early hematopoietic lineage restrictions directed by Ikaros

Nat Immunol. 2006 Apr;7(4):382-91. doi: 10.1038/ni1314. Epub 2006 Mar 5.

Abstract

Ikaros is expressed in early hematopoietic progenitors and is required for lymphoid differentiation. In the absence of Ikaros, there is a lack of markers defining fate restriction along lympho-myeloid pathways, but it is unclear whether formation of specific progenitors or expression of their markers is affected. Here we use a reporter based on Ikaros regulatory elements to separate early progenitors in wild-type and Ikaros-null mice. We found previously undetected Ikaros-null lympho-myeloid progenitors lacking the receptor tyrosine kinase Flt3 that were capable of myeloid but not lymphoid differentiation. In contrast, lack of Ikaros in the common myeloid progenitor resulted in increased formation of erythro-megakaryocytes at the expense of myeloid progenitors. Using this approach, we identify previously unknown pivotal functions for Ikaros in distinct fate 'decisions' in the early hematopoietic hierarchy.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Crosses, Genetic
  • Green Fluorescent Proteins
  • Hematopoiesis / immunology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology*
  • Ikaros Transcription Factor / immunology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology
  • Specific Pathogen-Free Organisms

Substances

  • Green Fluorescent Proteins
  • Ikaros Transcription Factor