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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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1998-01, Vol.95 (2), p.657-662 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Klug, Christopher A. Morrison, Sean J. Masek, Marilyn Hahm, Kyungmin Smale, Stephen T. Weissman, Irving L. |
| description | 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. |
| doi_str_mv | 10.1073/pnas.95.2.657 |
| format | Article |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.95.2.657</identifier><identifier>PMID: 9435248</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1998-01, Vol.95 (2), p.657-662</ispartof><rights>Copyright 1993-1998 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Jan 20, 1998</rights><rights>Copyright © 1998, The National Academy of Sciences 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c574t-852f74ce96f58beba822ed3a01627c3aaca8f3343bda67c28d6f95aeb45a21243</citedby><cites>FETCH-LOGICAL-c574t-852f74ce96f58beba822ed3a01627c3aaca8f3343bda67c28d6f95aeb45a21243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/95/2.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/44164$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/44164$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9435248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klug, Christopher A.</creatorcontrib><creatorcontrib>Morrison, Sean J.</creatorcontrib><creatorcontrib>Masek, Marilyn</creatorcontrib><creatorcontrib>Hahm, Kyungmin</creatorcontrib><creatorcontrib>Smale, Stephen T.</creatorcontrib><creatorcontrib>Weissman, Irving L.</creatorcontrib><title>Hematopoietic Stem Cells and Lymphoid Progenitors Express Different Ikaros Isoforms, and Ikaros is Localized to Heterochromatin in Immature Lymphocytes</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Biological Sciences</subject><subject>Cell Differentiation</subject><subject>Cell lines</subject><subject>Cell Nucleus - metabolism</subject><subject>Cellular biology</subject><subject>DNA-Binding Proteins</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Heterochromatin - metabolism</subject><subject>Heterochromatin - ultrastructure</subject><subject>Ikaros Transcription Factor</subject><subject>Immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes - cytology</subject><subject>Lymphocytes - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Multipotent stem cells</subject><subject>Myeloid cells</subject><subject>Neutrophils</subject><subject>Progenitor cells</subject><subject>Protein isoforms</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Stem cells</subject><subject>T lymphocytes</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk-r1DAUxYsoz_Hp0o0oBEFXdkzzp2nAjYxPZ2BAQV2HNL19k7FtapLKG7-IX9eMUwZ1oRBIyPmd3JvLybKHBV4WWNCX46DDUvIlWZZc3MoWBZZFXjKJb2cLjInIK0bY3exeCHuMseQVvsguJKOcsGqR_VhDr6MbnYVoDfoYoUcr6LqA9NCg7aEfd8426IN31zDY6HxAVzejhxDQG9u24GGIaPNFexfQJrjW-T68-OWdL21AW2d0Z79Dg6JDa4jgndl5l-raAaW16dNx8jCXM4cI4X52p9VdgAfzfpl9fnv1abXOt-_fbVavt7nhgsW84qQVzIAsW17VUOuKEGioxkVJhKFaG121lDJaN7oUhlRN2UquoWZck4Iwepm9Or07TnUPjUnf8bpTo7e99gfltFV_KoPdqWv3TRUVE2WyP5_t3n2dIETV22DS_PQAbgpKyFIwLsl_wdQvY2VFE_j0L3DvJj-kGSiCCyqo5EWC8hNk0oiDh_bccIHVMRXqmAoluSIqpSLxT37_5ZmeY5D0Z7N-tJ3V2a7aqesi3MTEPf4Hl-RHJ3kfUlLOOmNFyehPT-TXxw</recordid><startdate>19980120</startdate><enddate>19980120</enddate><creator>Klug, Christopher A.</creator><creator>Morrison, Sean J.</creator><creator>Masek, Marilyn</creator><creator>Hahm, Kyungmin</creator><creator>Smale, Stephen T.</creator><creator>Weissman, Irving L.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><general>The National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19980120</creationdate><title>Hematopoietic Stem Cells and Lymphoid Progenitors Express Different Ikaros Isoforms, and Ikaros is Localized to Heterochromatin in Immature Lymphocytes</title><author>Klug, Christopher A. ; Morrison, Sean J. ; Masek, Marilyn ; Hahm, Kyungmin ; Smale, Stephen T. ; Weissman, Irving L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c574t-852f74ce96f58beba822ed3a01627c3aaca8f3343bda67c28d6f95aeb45a21243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Biological Sciences</topic><topic>Cell Differentiation</topic><topic>Cell lines</topic><topic>Cell Nucleus - metabolism</topic><topic>Cellular biology</topic><topic>DNA-Binding Proteins</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Heterochromatin - metabolism</topic><topic>Heterochromatin - ultrastructure</topic><topic>Ikaros Transcription Factor</topic><topic>Immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes - cytology</topic><topic>Lymphocytes - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Multipotent stem cells</topic><topic>Myeloid cells</topic><topic>Neutrophils</topic><topic>Progenitor cells</topic><topic>Protein isoforms</topic><topic>Proteins</topic><topic>Rodents</topic><topic>Stem cells</topic><topic>T lymphocytes</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klug, Christopher A.</creatorcontrib><creatorcontrib>Morrison, Sean J.</creatorcontrib><creatorcontrib>Masek, Marilyn</creatorcontrib><creatorcontrib>Hahm, Kyungmin</creatorcontrib><creatorcontrib>Smale, Stephen T.</creatorcontrib><creatorcontrib>Weissman, Irving L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klug, Christopher A.</au><au>Morrison, Sean J.</au><au>Masek, Marilyn</au><au>Hahm, Kyungmin</au><au>Smale, Stephen T.</au><au>Weissman, Irving L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hematopoietic Stem Cells and Lymphoid Progenitors Express Different Ikaros Isoforms, and Ikaros is Localized to Heterochromatin in Immature Lymphocytes</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1998-01-20</date><risdate>1998</risdate><volume>95</volume><issue>2</issue><spage>657</spage><epage>662</epage><pages>657-662</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><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.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>9435248</pmid><doi>10.1073/pnas.95.2.657</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Hematopoietic Stem Cells and Lymphoid Progenitors Express Different Ikaros Isoforms, and Ikaros is Localized to Heterochromatin in Immature Lymphocytes |
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