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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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Submitted December 1, 2004
Accepted January 25, 2005

Tie2Cre mediated gene ablation defines the Stem Cell Leukemia gene (SCL/tal1)-dependent window during hematopoietic stem cell development

Thorsten M Schlaeger, Hanna K Mikkola, Christos Gekas, Hildur B Helgadottir, and Stuart H Orkin*

Division of Hematology-Oncology, Dana-Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, MA, USA
Division of Hematology-Oncology, Dana-Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA

* Corresponding author; email: stuart_orkin{at}dfci.harvard.edu.

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. 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, AGM (aorta-gonad-mesonephros-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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