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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3336-3341.
Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-06-1935.
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HEMATOPOIESIS
Stem cell leukemia protein directs hematopoietic stem cell fate
Atsushi Kunisato,
Shigeru Chiba,
Toshiki Saito,
Keiki Kumano,
Etsuko Nakagami-Yamaguchi,
Tomoyuki Yamaguchi, and
Hisamaru Hirai
From the Departments of Hematology/Oncology and Cell Therapy/Transplantation Medicine, Graduate School of Medicine, University of Tokyo, Japan.
Stem cell leukemia (SCL) protein has been shown to be an essential transcription factor during hematopoietic development in the embryo. In adult hematopoiesis, however, the role for SCL has remained largely unknown, whereas it is expressed in bone marrow hematopoietic stem cells (HSCs). In this study, we performed HSC transplantation and an in vitro HSC differentiation assay using retrovirally transduced HSCs with wild-type (WT) and dominant-negative (DN) SCL. The transplantation experiments showed that SCL does not affect the long-term repopulating capacity of HSCs but that WT SCL and DN SCL increase the short-term contribution of the transduced HSCs in myeloid and lymphoid lineages, respectively. An in vitro single-cell assay using a fetal thymus organ culture system further demonstrated that WT SCL facilitates HSCs to differentiate into the myeloid lineage but that DN SCL facilitates HSCs to differentiate into the lymphoid lineage. We conclude that the up-regulation or down-regulation of SCL directs HSCs toward myeloid or lymphoid lineage, respectively, although SCL does not affect their long-term repopulating capacity. (Blood. 2004;103: 3336-3341)

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