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Hematopoietic stem cell fate is established by the Notch-Runx pathway
Identifying the molecular pathways regulating hematopoietic stem cell (HSC) specification, self-renewal, and expansion remains a fundamental goal of both basic and clinical biology. Here, we analyzed the effects of Notch signaling on HSC number during zebrafish development and adulthood, defining a...
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| Published in: | Genes & development 2005-10, Vol.19 (19), p.2331-2342 |
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| creator | Burns, Caroline Erter Traver, David Mayhall, Elizabeth Shepard, Jennifer L Zon, Leonard I |
| description | Identifying the molecular pathways regulating hematopoietic stem cell (HSC) specification, self-renewal, and expansion remains a fundamental goal of both basic and clinical biology. Here, we analyzed the effects of Notch signaling on HSC number during zebrafish development and adulthood, defining a critical pathway for stem cell specification. The Notch signaling mutant mind bomb displays normal embryonic hematopoiesis but fails to specify adult HSCs. Surprisingly, transient Notch activation during embryogenesis via an inducible transgenic system led to a Runx1-dependent expansion of HSCs in the aorta-gonad-mesonephros (AGM) region. In irradiated adults, Notch activity induced runx1 gene expression and increased multilineage hematopoietic precursor cells approximately threefold in the marrow. This increase was followed by the accelerated recovery of all the mature blood cell lineages. These data define the Notch-Runx pathway as critical for the developmental specification of HSC fate and the subsequent homeostasis of HSC number, thus providing a mechanism for amplifying stem cells in vivo. |
| doi_str_mv | 10.1101/gad.1337005 |
| format | article |
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These data define the Notch-Runx pathway as critical for the developmental specification of HSC fate and the subsequent homeostasis of HSC number, thus providing a mechanism for amplifying stem cells in vivo.</description><subject>Animals</subject><subject>Aorta - cytology</subject><subject>Aorta - physiology</subject><subject>Blood Cells - cytology</subject><subject>Blood Cells - physiology</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Lineage - physiology</subject><subject>Cell Lineage - radiation effects</subject><subject>Core Binding Factor Alpha 2 Subunit - genetics</subject><subject>Core Binding Factor Alpha 2 Subunit - metabolism</subject><subject>Danio rerio</subject><subject>Embryonic Development - physiology</subject><subject>Embryonic Development - radiation effects</subject><subject>Gamma Rays</subject><subject>Gene Expression Regulation, Developmental - physiology</subject><subject>Gene Expression Regulation, Developmental - radiation effects</subject><subject>Gonads - cytology</subject><subject>Gonads - physiology</subject><subject>Hematopoiesis - physiology</subject><subject>Hematopoiesis - radiation effects</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Homeostasis - physiology</subject><subject>Homeostasis - radiation effects</subject><subject>Mesonephros - cytology</subject><subject>Mesonephros - physiology</subject><subject>Mutation</subject><subject>Research Papers</subject><subject>Whole-Body Irradiation - methods</subject><subject>Zebrafish - anatomy & histology</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish - genetics</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - metabolism</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkU1Lw0AQhhdRbK2evMuevEjqbDbZ3VwEKdUKoiB6XiabTRPJl9mt2n9vSosfJ08zMA8P8_IScspgyhiwyyVmU8a5BIj3yJjFURLEkZT7ZAwqgSDhIhmRI-deAUCAEIdkxAQTgstwTOYLW6Nvu7a0vjTUeVtTY6uK5ugtLR21zmNala6wGU3X1BeWPrTeFMHTqvmkHfriA9fH5CDHytmT3ZyQl5v582wR3D_e3s2u7wMTSeGDjKWKMynjUGVoRGwZZFKliCo0CHGO3CYqzI0ArnJIhyVKFCgUwgiLOeMTcrX1dqu0tpmxje-x0l1f1tivdYul_ntpykIv23fNwgggCgfB-U7Qt2-rIZuuS7fJi41tV04LJeIoEvxfkEmu5NZ4sQVN3zrX2_z7GwZ6048e-tG7fgb67HeAH3ZXCP8C6WSMXA</recordid><startdate>20051001</startdate><enddate>20051001</enddate><creator>Burns, Caroline Erter</creator><creator>Traver, David</creator><creator>Mayhall, Elizabeth</creator><creator>Shepard, Jennifer L</creator><creator>Zon, Leonard I</creator><general>Cold Spring Harbor Laboratory Press</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20051001</creationdate><title>Hematopoietic stem cell fate is established by the Notch-Runx pathway</title><author>Burns, Caroline Erter ; Traver, David ; Mayhall, Elizabeth ; Shepard, Jennifer L ; Zon, Leonard I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c476t-d1b83177528dac65e10d78baa82ca05fa3e982fc6038f0bfc649808a66c6eaf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Aorta - cytology</topic><topic>Aorta - physiology</topic><topic>Blood Cells - cytology</topic><topic>Blood Cells - physiology</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Lineage - physiology</topic><topic>Cell Lineage - radiation effects</topic><topic>Core Binding Factor Alpha 2 Subunit - genetics</topic><topic>Core Binding Factor Alpha 2 Subunit - metabolism</topic><topic>Danio rerio</topic><topic>Embryonic Development - physiology</topic><topic>Embryonic Development - radiation effects</topic><topic>Gamma Rays</topic><topic>Gene Expression Regulation, Developmental - physiology</topic><topic>Gene Expression Regulation, Developmental - radiation effects</topic><topic>Gonads - cytology</topic><topic>Gonads - physiology</topic><topic>Hematopoiesis - physiology</topic><topic>Hematopoiesis - radiation effects</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Homeostasis - physiology</topic><topic>Homeostasis - radiation effects</topic><topic>Mesonephros - cytology</topic><topic>Mesonephros - physiology</topic><topic>Mutation</topic><topic>Research Papers</topic><topic>Whole-Body Irradiation - methods</topic><topic>Zebrafish - anatomy & histology</topic><topic>Zebrafish - embryology</topic><topic>Zebrafish - genetics</topic><topic>Zebrafish Proteins - genetics</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burns, Caroline Erter</creatorcontrib><creatorcontrib>Traver, David</creatorcontrib><creatorcontrib>Mayhall, Elizabeth</creatorcontrib><creatorcontrib>Shepard, Jennifer L</creatorcontrib><creatorcontrib>Zon, Leonard I</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burns, Caroline Erter</au><au>Traver, David</au><au>Mayhall, Elizabeth</au><au>Shepard, Jennifer L</au><au>Zon, Leonard I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hematopoietic stem cell fate is established by the Notch-Runx pathway</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2005-10-01</date><risdate>2005</risdate><volume>19</volume><issue>19</issue><spage>2331</spage><epage>2342</epage><pages>2331-2342</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>Identifying the molecular pathways regulating hematopoietic stem cell (HSC) specification, self-renewal, and expansion remains a fundamental goal of both basic and clinical biology. Here, we analyzed the effects of Notch signaling on HSC number during zebrafish development and adulthood, defining a critical pathway for stem cell specification. The Notch signaling mutant mind bomb displays normal embryonic hematopoiesis but fails to specify adult HSCs. Surprisingly, transient Notch activation during embryogenesis via an inducible transgenic system led to a Runx1-dependent expansion of HSCs in the aorta-gonad-mesonephros (AGM) region. In irradiated adults, Notch activity induced runx1 gene expression and increased multilineage hematopoietic precursor cells approximately threefold in the marrow. This increase was followed by the accelerated recovery of all the mature blood cell lineages. 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| subjects | Animals Aorta - cytology Aorta - physiology Blood Cells - cytology Blood Cells - physiology Cell Differentiation - physiology Cell Lineage - physiology Cell Lineage - radiation effects Core Binding Factor Alpha 2 Subunit - genetics Core Binding Factor Alpha 2 Subunit - metabolism Danio rerio Embryonic Development - physiology Embryonic Development - radiation effects Gamma Rays Gene Expression Regulation, Developmental - physiology Gene Expression Regulation, Developmental - radiation effects Gonads - cytology Gonads - physiology Hematopoiesis - physiology Hematopoiesis - radiation effects Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Homeostasis - physiology Homeostasis - radiation effects Mesonephros - cytology Mesonephros - physiology Mutation Research Papers Whole-Body Irradiation - methods Zebrafish - anatomy & histology Zebrafish - embryology Zebrafish - genetics Zebrafish Proteins - genetics Zebrafish Proteins - metabolism |
| title | Hematopoietic stem cell fate is established by the Notch-Runx pathway |
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