Hematopoietic Stem Cells and Lymphoid Progenitors Express Different Ikaros Isoforms, and Ikaros is Localized to Heterochromatin in Immature Lymphocytes

The generation of lymphoid cells in mice depends on the function of the Ikaros protein. Ikaros has been characterized as a lymphoid-restricted, zinc-finger transcription factor that is derived from an alternatively spliced message. Ikaros knockout mice have defects in multiple cell lineages, raising...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-01, Vol.95 (2), p.657-662
Main Authors: Klug, Christopher A., Morrison, Sean J., Masek, Marilyn, Hahm, Kyungmin, Smale, Stephen T., Weissman, Irving L.
Format: Article
Language:English
Subjects:
Animals
Antibodies
Biological Sciences
Cell Differentiation
Cell lines
Cell Nucleus - metabolism
Cellular biology
DNA-Binding Proteins
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Heterochromatin - metabolism
Heterochromatin - ultrastructure
Ikaros Transcription Factor
Immunology
Lymphocytes
Lymphocytes - cytology
Lymphocytes - metabolism
Mice
Mice, Inbred C57BL
Multipotent stem cells
Myeloid cells
Neutrophils
Progenitor cells
Protein isoforms
Proteins
Rodents
Stem cells
T lymphocytes
Transcription Factors - biosynthesis
Transcription Factors - genetics
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Summary:The generation of lymphoid cells in mice depends on the function of the Ikaros protein. Ikaros has been characterized as a lymphoid-restricted, zinc-finger transcription factor that is derived from an alternatively spliced message. Ikaros knockout mice have defects in multiple cell lineages, raising the question of whether the protein regulates multiple committed progenitors and/or multipotent stem cells. To address this issue, we examined Ikaros expression in purified populations of multipotent cells and more committed progenitors. We found that the DNA-binding isoforms of Ikaros were localized in the nucleus of the most primitive hematopoietic stem cell subset. Changes in the RNA splicing pattern of Ikaros occurred at two stages: (i) as long-term self-renewing stem cells differentiated into short-term self-renewing stem cells and (ii) as non-self-renewing multipotent progenitors differentiated into lymphoid-committed progenitors. Unexpectedly, we found Ikaros localized to heterochromatin in Abelson-transformed pre-B lymphocytes by using immunogold electron microscopy. These observations suggest a complex role for Ikaros in lymphoid development.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.2.657