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Blood, 5 February 2009, Vol. 113, No. 6, pp. 1241-1249. Prepublished online as a Blood First Edition Paper on October 16, 2008; DOI 10.1182/blood-2008-04-149898.
Submitted April 4, 2008
Department of Molecular Medicine & Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand * Corresponding author; email: m.flores{at}auckland.ac.nz.
The transcription factor Runx1 is essential for the development of definitive hematopoietic stem cells (HSCs) during vertebrate embryogenesis and is transcribed from two promoters, P1 and P2, generating two major Runx1 isoforms. We have created two stable runx1 promoter zebrafish transgenic lines that provide insight into the roles of the P1 and P2 isoforms during the establishment of definitive hematopoiesis. The Tg(runx1P1:EGFP) line displays fluorescence in the posterior blood island, where definitive erythromyeloid progenitors develop. The Tg(runx1P2:EGFP) line marks definitive HSCs in the aorta-gonad-mesonephros (AGM), with EGFP-labeled cells later populating the pronephros and thymus. This suggests that a function of runx1 promoter switching is associated with the establishment of discrete definitive blood progenitor compartments. These runx1 promoter transgenic lines are novel tools for the study of Runx1 regulation and function in normal and malignant hematopoiesis. The ability to visualize and isolate fluorescently-labeled HSCs should contribute to further elucidating the complex regulation of HSC development.
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