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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3871-3874.
Prepublished online as a Blood First Edition Paper on January 27, 2005; DOI 10.1182/blood-2004-11-4467.
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HEMATOPOIESIS Brief report
Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)dependent window during hematopoietic stem-cell development
Thorsten M. Schlaeger,
Hanna K. A. Mikkola,
Christos Gekas,
Hildur B. Helgadottir, and
Stuart H. Orkin
From the Division of Hematology-Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School; and Howard Hughes Medical Institute (HHMI), Boston, MA.
The stem-cell leukemia gene (SCL/tal1) is essential for the formation of all blood lineages. SCL is first expressed in mesodermal cells that give rise to embryonic blood cells, and continues to be expressed in fetal and adult hematopoietic stem cells (HSCs). However, SCL is not required for the maintenance of established long-term repopulating (LTR) HSCs in the adult. The time point at which HSC development becomes SCL independent has not been defined. Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains2 (Tie2) expression appears in hemogenic and vasculogenic sites shortly after SCL. We therefore used the Tie2Cre mouse to inactivate SCL early during embryonic and fetal hematopoiesis. Tie2Cre completely inactivated SCL in yolk sac, the aortagonad-mesonephros (AGM) region, and fetal liver hematopoietic cells and circulating blood cells. However, the fetal liver was colonized by functional LTR-HSCs. Yet SCL remained crucial for proper differentiation of both primitive and definitive red cells and megakaryocytes. These results indicate that the SCL-dependent phase of HSC development ends before Tie2Cre-mediated gene ablation becomes effective.

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