A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification
The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute iymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specifi...
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| Veröffentlicht in: | Cell research 2012-06, Vol.22 (6), p.986-1002 |
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| creator | Bueno, Clara Montes, Rosa Melen, Gustavo J Ramos-Mejia, Verónica Real, Pedro J Ayllón, Verónica Sanchez, Laura Ligero, Gertrudis Gutierrez-Aranda, Iván Fernández, Agustín F Fraga, Mario F Moreno-Gimeno, Inmaculada Burks, Deborah del Carmen Plaza-Calonge, María Rodríguez-Manzaneque, Juan C Menendez, Pablo |
| description | The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute iymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells （hESCs）. Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs |
| doi_str_mv | 10.1038/cr.2012.4 |
| format | Article |
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Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells （hESCs）. Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs</description><identifier>ISSN: 1001-0602</identifier><identifier>EISSN: 1748-7838</identifier><identifier>DOI: 10.1038/cr.2012.4</identifier><identifier>PMID: 22212479</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/199 ; 631/250/232 ; 631/67/1990/283 ; Biomedical and Life Sciences ; Cell Biology ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Endothelial Cells - cytology ; Gene Expression Profiling ; Hematopoiesis ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Infants ; Leukemia ; Life Sciences ; Myeloid-Lymphoid Leukemia Protein - genetics ; Myeloid-Lymphoid Leukemia Protein - metabolism ; Oncogene Proteins, Fusion - genetics ; Oncogene Proteins, Fusion - metabolism ; Original ; original-article ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Protein Precursors - genetics ; Protein Precursors - metabolism ; Signal Transduction ; Stem cells ; Up-Regulation ; 人类胚胎干细胞 ; 内皮 ; 基因表达谱 ; 早期 ; 模型 ; 白血病 ; 融合基因 ; 造血</subject><ispartof>Cell research, 2012-06, Vol.22 (6), p.986-1002</ispartof><rights>Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2012</rights><rights>Copyright Nature Publishing Group Jun 2012</rights><rights>Copyright © 2012 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2012 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-fc7f1d9db342857a21c158cee4512b7b10d162178cc4cc2452346cc00f1acc113</citedby><cites>FETCH-LOGICAL-c431t-fc7f1d9db342857a21c158cee4512b7b10d162178cc4cc2452346cc00f1acc113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/85240X/85240X.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367544/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367544/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22212479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bueno, Clara</creatorcontrib><creatorcontrib>Montes, Rosa</creatorcontrib><creatorcontrib>Melen, Gustavo J</creatorcontrib><creatorcontrib>Ramos-Mejia, Verónica</creatorcontrib><creatorcontrib>Real, Pedro J</creatorcontrib><creatorcontrib>Ayllón, Verónica</creatorcontrib><creatorcontrib>Sanchez, Laura</creatorcontrib><creatorcontrib>Ligero, Gertrudis</creatorcontrib><creatorcontrib>Gutierrez-Aranda, Iván</creatorcontrib><creatorcontrib>Fernández, Agustín F</creatorcontrib><creatorcontrib>Fraga, Mario F</creatorcontrib><creatorcontrib>Moreno-Gimeno, Inmaculada</creatorcontrib><creatorcontrib>Burks, Deborah</creatorcontrib><creatorcontrib>del Carmen Plaza-Calonge, María</creatorcontrib><creatorcontrib>Rodríguez-Manzaneque, Juan C</creatorcontrib><creatorcontrib>Menendez, Pablo</creatorcontrib><title>A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification</title><title>Cell research</title><addtitle>Cell Res</addtitle><addtitle>Cell Research</addtitle><description>The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute iymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells （hESCs）. Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs</description><subject>631/208/199</subject><subject>631/250/232</subject><subject>631/67/1990/283</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Endothelial Cells - cytology</subject><subject>Gene Expression Profiling</subject><subject>Hematopoiesis</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Infants</subject><subject>Leukemia</subject><subject>Life Sciences</subject><subject>Myeloid-Lymphoid Leukemia Protein - genetics</subject><subject>Myeloid-Lymphoid Leukemia Protein - metabolism</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Oncogene Proteins, Fusion - 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Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells （hESCs）. Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22212479</pmid><doi>10.1038/cr.2012.4</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell research, 2012-06, Vol.22 (6), p.986-1002 |
| issn | 1001-0602 1748-7838 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | 631/208/199 631/250/232 631/67/1990/283 Biomedical and Life Sciences Cell Biology Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Endothelial Cells - cytology Gene Expression Profiling Hematopoiesis Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Infants Leukemia Life Sciences Myeloid-Lymphoid Leukemia Protein - genetics Myeloid-Lymphoid Leukemia Protein - metabolism Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - metabolism Original original-article Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Protein Precursors - genetics Protein Precursors - metabolism Signal Transduction Stem cells Up-Regulation 人类胚胎干细胞 内皮 基因表达谱 早期 模型 白血病 融合基因 造血 |
| title | A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification |
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