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    The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis.

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    Authors
    Sroczynska, Patrycja
    Lancrin, Christophe
    Kouskoff, Valerie
    Lacaud, Georges
    Affiliation
    Cancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.
    Issue Date
    2009-12-17
    
    Metadata
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    Abstract
    The transcription factor RUNX1/AML1 is a master regulator of hematopoietic development. Its spatiotemporal expression is tightly regulated during embryonic development and is under the control of 2 alternative promoters, distal and proximal. Despite the functional significance of Runx1, the relative and specific activities of these 2 promoters remain largely uncharacterized. To investigate these activities, we introduced 2 reporter genes under the control of the proximal and distal promoters in embryonic stem cell and transgenic mouse lines. Our study reveals that both in vitro and in vivo the proximal Runx1 isoform marks a hemogenic endothelium cell population, whereas the subsequent expression of distal Runx1 defines fully committed definitive hematopoietic progenitors. Interestingly, hematopoietic commitment in distal Runx1 knockout embryos appears normal. Altogether, our data demonstrate that the differential activities of the 2 Runx1 promoters define milestones of hematopoietic development and suggest that the proximal isoform plays a critical role in the generation of hematopoietic cells from hemogenic endothelium. Identification and access to the discrete stages of hematopoietic development defined by the activities of the Runx1 promoters will provide the opportunity to further explore the cellular and molecular mechanisms of hematopoietic development.
    Citation
    The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis. 2009, 114 (26):5279-89 Blood
    Journal
    Blood
    URI
    http://hdl.handle.net/10541/91615
    DOI
    10.1182/blood-2009-05-222307
    PubMed ID
    19858498
    Language
    en
    ISSN
    1528-0020
    ae974a485f413a2113503eed53cd6c53
    10.1182/blood-2009-05-222307
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research
    Stem Cell and Haematopoiesis
    Stem Cell Biology

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