Alternative Runx1 promoter usage in mouse developmental hematopoiesis
The interest in stem cell based therapies has emphasized the importance of understanding the cellular and molecular mechanisms by which stem cells are generated in ontogeny and maintained throughout adult life. Hematopoietic stem cells (HSCs) are first found in clusters of hematopoietic cells buddin...
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| Veröffentlicht in: | Blood cells, molecules, & diseases molecules, & diseases, 2009-07, Vol.43 (1), p.35-42 |
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| creator | Bee, Thomas Liddiard, Kate Swiers, Gemma Bickley, Sorrel R.B. Vink, Chris S. Jarratt, Andrew Hughes, Jim R. Medvinsky, Alexander de Bruijn, Marella F.T.R. |
| description | The interest in stem cell based therapies has emphasized the importance of understanding the cellular and molecular mechanisms by which stem cells are generated in ontogeny and maintained throughout adult life. Hematopoietic stem cells (HSCs) are first found in clusters of hematopoietic cells budding from the luminal wall of the major arteries in the developing mammalian embryo. The transcription factor Runx1 is critical for their generation and is specifically expressed at sites of HSC generation, prior to their formation. To understand better the transcriptional hierarchies that converge on
Runx1 during HSC emergence, we have initiated studies into its transcriptional regulation. Here we systematically analyzed
Runx1 P1 and P2 alternative promoter usage in hematopoietic sites and in sorted cell populations during mouse hematopoietic development. Our results indicate that
Runx1 expression in primitive erythrocytes is largely P2-derived, whilst in definitive hematopoietic stem and/or progenitor cells from the yolk sac or AGM and vitelline and umbilical arteries both the distal P1 and proximal P2 promoters are active. After cells have migrated to the fetal liver, the P1 gradually becomes the main hematopoietic promoter and remains this into adulthood. In addition, we identified a novel P2-derived
Runx1 isoform. |
| doi_str_mv | 10.1016/j.bcmd.2009.03.011 |
| format | Article |
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Runx1 during HSC emergence, we have initiated studies into its transcriptional regulation. Here we systematically analyzed
Runx1 P1 and P2 alternative promoter usage in hematopoietic sites and in sorted cell populations during mouse hematopoietic development. Our results indicate that
Runx1 expression in primitive erythrocytes is largely P2-derived, whilst in definitive hematopoietic stem and/or progenitor cells from the yolk sac or AGM and vitelline and umbilical arteries both the distal P1 and proximal P2 promoters are active. After cells have migrated to the fetal liver, the P1 gradually becomes the main hematopoietic promoter and remains this into adulthood. In addition, we identified a novel P2-derived
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Runx1 during HSC emergence, we have initiated studies into its transcriptional regulation. Here we systematically analyzed
Runx1 P1 and P2 alternative promoter usage in hematopoietic sites and in sorted cell populations during mouse hematopoietic development. Our results indicate that
Runx1 expression in primitive erythrocytes is largely P2-derived, whilst in definitive hematopoietic stem and/or progenitor cells from the yolk sac or AGM and vitelline and umbilical arteries both the distal P1 and proximal P2 promoters are active. After cells have migrated to the fetal liver, the P1 gradually becomes the main hematopoietic promoter and remains this into adulthood. In addition, we identified a novel P2-derived
Runx1 isoform.</description><subject>Animals</subject><subject>Aorta - cytology</subject><subject>Aorta - embryology</subject><subject>Aorta - physiology</subject><subject>Base Sequence</subject><subject>Core Binding Factor Alpha 2 Subunit - genetics</subject><subject>Core Binding Factor Alpha 2 Subunit - metabolism</subject><subject>Development</subject><subject>Female</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Hematopoiesis</subject><subject>Hematopoietic stem and progenitor cells</subject><subject>Humans</subject><subject>Liver - cytology</subject><subject>Liver - embryology</subject><subject>Liver - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mouse</subject><subject>Placenta - cytology</subject><subject>Placenta - embryology</subject><subject>Placenta - physiology</subject><subject>Pregnancy</subject><subject>Promoter Regions, Genetic</subject><subject>Runx1</subject><subject>Sequence Alignment</subject><subject>Transcription, Genetic</subject><subject>Transcriptional regulation</subject><subject>Yolk Sac - cytology</subject><subject>Yolk Sac - embryology</subject><subject>Yolk Sac - physiology</subject><issn>1079-9796</issn><issn>1096-0961</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMo7rr6BzxIT95ak2aTNOBlWdYPWBBEzyFNppqlaWvTLvrvTdkFbx6GGYZ33pl5ELomOCOY8LtdVhpvsxxjmWGaYUJO0JxgydMY5HSqhUylkHyGLkLYYRwlsjhHMyKXfJkTNkebVT1A3-jB7SF5HZtvknR969vYTMagPyBxTeLbMUBiYQ9123loBl0nn-D10Hatg-DCJTqrdB3g6pgX6P1h87Z-Srcvj8_r1TY1lC2HlNkKS8woxRWGighBCNUFpYUURgotZVHpkkJFudaspExaUXLLmSxyzRjhdIFuD77xxq8RwqC8CwbqWjcQb1Rc0FxMGxYoPwhN34bQQ6W63nnd_yiC1QRP7dQET03wFKYqkolDN0f3sfRg_0aOtKLg_iCA-OPeQa-CcdAYsK4HMyjbuv_8fwFXN4AX</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Bee, Thomas</creator><creator>Liddiard, Kate</creator><creator>Swiers, Gemma</creator><creator>Bickley, Sorrel R.B.</creator><creator>Vink, Chris S.</creator><creator>Jarratt, Andrew</creator><creator>Hughes, Jim R.</creator><creator>Medvinsky, Alexander</creator><creator>de Bruijn, Marella F.T.R.</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20090701</creationdate><title>Alternative Runx1 promoter usage in mouse developmental hematopoiesis</title><author>Bee, Thomas ; 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Hematopoietic stem cells (HSCs) are first found in clusters of hematopoietic cells budding from the luminal wall of the major arteries in the developing mammalian embryo. The transcription factor Runx1 is critical for their generation and is specifically expressed at sites of HSC generation, prior to their formation. To understand better the transcriptional hierarchies that converge on
Runx1 during HSC emergence, we have initiated studies into its transcriptional regulation. Here we systematically analyzed
Runx1 P1 and P2 alternative promoter usage in hematopoietic sites and in sorted cell populations during mouse hematopoietic development. Our results indicate that
Runx1 expression in primitive erythrocytes is largely P2-derived, whilst in definitive hematopoietic stem and/or progenitor cells from the yolk sac or AGM and vitelline and umbilical arteries both the distal P1 and proximal P2 promoters are active. After cells have migrated to the fetal liver, the P1 gradually becomes the main hematopoietic promoter and remains this into adulthood. In addition, we identified a novel P2-derived
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| subjects | Animals Aorta - cytology Aorta - embryology Aorta - physiology Base Sequence Core Binding Factor Alpha 2 Subunit - genetics Core Binding Factor Alpha 2 Subunit - metabolism Development Female Gene Expression Regulation, Developmental Hematopoiesis Hematopoietic stem and progenitor cells Humans Liver - cytology Liver - embryology Liver - physiology Male Mice Mice, Inbred C57BL Mouse Placenta - cytology Placenta - embryology Placenta - physiology Pregnancy Promoter Regions, Genetic Runx1 Sequence Alignment Transcription, Genetic Transcriptional regulation Yolk Sac - cytology Yolk Sac - embryology Yolk Sac - physiology |
| title | Alternative Runx1 promoter usage in mouse developmental hematopoiesis |
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