Early hematopoietic lineage restrictions directed by Ikaros

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 marker...

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Bibliographic Details
Published in:Nature Immunology 2006-04, Vol.7 (4), p.382-391
Main Authors: Georgopoulos, Katia, Yoshida, Toshimi, Yao-Ming Ng, Samuel, Zuniga-Pflucker, Juan Carlos
Format: Article
Language:English
Subjects:
Animals
Biomedical and Life Sciences
Biomedicine
Cell Differentiation - immunology
Crosses, Genetic
Green Fluorescent Proteins
Hematopoiesis - immunology
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - immunology
Ikaros Transcription Factor - immunology
Immunology
Infectious Diseases
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Fluorescence
Myeloid Cells - cytology
Myeloid Cells - immunology
Specific Pathogen-Free Organisms
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Summary: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.
ISSN:1529-2908
1529-2916
1365-2567
DOI:10.1038/ni1314