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Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes

Klug, Christopher A. and Morrison, Sean J. and Masek, Marilyn and Hahm, Kyungmin and Smale, Stephen T. and Weissman, Irving L. (1998) Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proceedings of the National Academy of Sciences of the United States of America, 95 (2). pp. 657-662. ISSN 0027-8424. PMCID PMC18476. http://resolver.caltech.edu/CaltechAUTHORS:20141202-112044031

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Abstract

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.


Item Type:Article
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URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.95.2.657DOIArticle
http://www.pnas.org/content/95/2/657PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18476/PubMed CentralArticle
Additional Information:© 1998 The National Academy of Sciences. Contributed by Irving L. Weissman, November 7, 1997. We express our appreciation to Amanda Fisher, Brad Cobb, Hewson Swift, and members of the Weissman lab for stimulating discussion. We thank Koichi Akashi and Motonari Kondo for communicating unpublished data and Doug Wright, David Traver, and Eric Lagasse for critical reading of the manuscript. Thanks to Libuse Jerabek for laboratory management, Veronica Braunstein for antibody preparation, Tim Knaak for FACS operation, Phil Verzola for photography, and L. Hidalgo for animal care. Sean Morrison was a predoctoral fellow with the Howard Hughes Medical Institute and Christopher Klug is a fellow of the Irvington Institute. This work was supported by National Cancer Institute Grant CA 42551 and a grant from SyStemixy Sandoz.
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Funding AgencyGrant Number
National Cancer Institute42551
SyStemixy/SandozUNSPECIFIED
PubMed Central ID:PMC18476
Record Number:CaltechAUTHORS:20141202-112044031
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20141202-112044031
Official Citation:Klug, C. A., Morrison, S. J., Masek, M., Hahm, K., Smale, S. T., & Weissman, I. L. (1998). Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proceedings of the National Academy of Sciences, 95(2), 657-662.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52269
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:02 Dec 2014 21:14
Last Modified:03 Nov 2017 23:12

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