AF10 plays a key role in the survival of uncommitted hematopoietic cells
Hematopoiesis is a complex process regulated by both cell intrinsic and cell extrinsic factors. Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases...
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| Veröffentlicht in: | PloS one 2012-12, Vol.7 (12), p.e51626-e51626 |
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| creator | Chamorro-Garcia, Raquel Cervera, Margarita Arredondo, Juan J |
| description | Hematopoiesis is a complex process regulated by both cell intrinsic and cell extrinsic factors. Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases. AF10 is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. The link between AF10 and leukemia, together with the known interactions between AF10 and hematopoietic regulators, suggests that AF10 may be important in hematopoiesis and in leukemic transformation. Here we show that AF10 is important for proper hematopoietic differentiation. The induction of hematopoietic differentiation in both human hematopoietic cell lines and murine total bone marrow cells triggers a decrease of AF10 mRNA and protein levels, particularly in stem cells and multipotent progenitors. Gain- and loss-of-function studies demonstrate that over- or under-expression of AF10 leads to apoptotic cell death in stem cells and multipotent progenitors. We conclude that AF10 plays a key role in the maintenance of multipotent hematopoietic cells. |
| doi_str_mv | 10.1371/journal.pone.0051626 |
| format | Article |
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Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases. AF10 is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. The link between AF10 and leukemia, together with the known interactions between AF10 and hematopoietic regulators, suggests that AF10 may be important in hematopoiesis and in leukemic transformation. Here we show that AF10 is important for proper hematopoietic differentiation. The induction of hematopoietic differentiation in both human hematopoietic cell lines and murine total bone marrow cells triggers a decrease of AF10 mRNA and protein levels, particularly in stem cells and multipotent progenitors. Gain- and loss-of-function studies demonstrate that over- or under-expression of AF10 leads to apoptotic cell death in stem cells and multipotent progenitors. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Chamorro-Garcia et al 2012 Chamorro-Garcia et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-9ffda1ba254b06deb305ea9d377337bf42dad63c9f907d5fa89d754a28eef4f23</citedby><cites>FETCH-LOGICAL-c692t-9ffda1ba254b06deb305ea9d377337bf42dad63c9f907d5fa89d754a28eef4f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526614/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526614/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23284727$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bunting, Kevin D.</contributor><creatorcontrib>Chamorro-Garcia, Raquel</creatorcontrib><creatorcontrib>Cervera, Margarita</creatorcontrib><creatorcontrib>Arredondo, Juan J</creatorcontrib><title>AF10 plays a key role in the survival of uncommitted hematopoietic cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hematopoiesis is a complex process regulated by both cell intrinsic and cell extrinsic factors. Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases. AF10 is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. The link between AF10 and leukemia, together with the known interactions between AF10 and hematopoietic regulators, suggests that AF10 may be important in hematopoiesis and in leukemic transformation. Here we show that AF10 is important for proper hematopoietic differentiation. The induction of hematopoietic differentiation in both human hematopoietic cell lines and murine total bone marrow cells triggers a decrease of AF10 mRNA and protein levels, particularly in stem cells and multipotent progenitors. Gain- and loss-of-function studies demonstrate that over- or under-expression of AF10 leads to apoptotic cell death in stem cells and multipotent progenitors. We conclude that AF10 plays a key role in the maintenance of multipotent hematopoietic cells.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Blotting, Western</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Cancer genetics</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Cell Differentiation</subject><subject>Cell growth</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>Chromosome rearrangements</subject><subject>Differentiation (biology)</subject><subject>Drosophila</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic transformation</subject><subject>Hematopoiesis</subject><subject>Hemopoiesis</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Insects</subject><subject>Leukemia</subject><subject>Leukemia - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chamorro-Garcia, Raquel</au><au>Cervera, Margarita</au><au>Arredondo, Juan J</au><au>Bunting, Kevin D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AF10 plays a key role in the survival of uncommitted hematopoietic cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-12-19</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e51626</spage><epage>e51626</epage><pages>e51626-e51626</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Hematopoiesis is a complex process regulated by both cell intrinsic and cell extrinsic factors. Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases. AF10 is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. The link between AF10 and leukemia, together with the known interactions between AF10 and hematopoietic regulators, suggests that AF10 may be important in hematopoiesis and in leukemic transformation. Here we show that AF10 is important for proper hematopoietic differentiation. The induction of hematopoietic differentiation in both human hematopoietic cell lines and murine total bone marrow cells triggers a decrease of AF10 mRNA and protein levels, particularly in stem cells and multipotent progenitors. Gain- and loss-of-function studies demonstrate that over- or under-expression of AF10 leads to apoptotic cell death in stem cells and multipotent progenitors. We conclude that AF10 plays a key role in the maintenance of multipotent hematopoietic cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23284727</pmid><doi>10.1371/journal.pone.0051626</doi><tpages>e51626</tpages><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Apoptosis Biology Blotting, Western Bone marrow Bone Marrow Cells - cytology Bone Marrow Cells - metabolism Cancer genetics Cell cycle Cell death Cell Differentiation Cell growth Cell Proliferation Cell Survival Cells, Cultured Chromosome rearrangements Differentiation (biology) Drosophila Flow Cytometry Fluorescent Antibody Technique Gene expression Genes Genetic transformation Hematopoiesis Hemopoiesis Homeostasis Humans Insects Leukemia Leukemia - metabolism Leukemia - pathology Medicine Mice Proteins Real-Time Polymerase Chain Reaction Regulators Reverse Transcriptase Polymerase Chain Reaction RNA RNA, Messenger - genetics RNA, Small Interfering - genetics Rodents Stem cell transplantation Stem cells Stem Cells - cytology Stem Cells - metabolism Transcription Factors - antagonists & inhibitors Transcription Factors - genetics Transcription Factors - metabolism Transformation |
| title | AF10 plays a key role in the survival of uncommitted hematopoietic cells |
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