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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.
Submitted June 18, 2003
Accepted December 19, 2003
Stem cell leukemia (SCL) directs hematopoietic stem cell fate
Atsushi Kunisato, Shigeru Chiba*, Toshiki Saito, Keiki Kumano, Etsuko Nakagami-Yamaguchi, Tomoyuki Yamaguchi, and Hisamaru Hirai
Departments of Hematology/Oncology and Cell Therapy/Transplantation Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
* Corresponding author; email: schiba-tky{at}umin.ac.jp.
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 while 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 transplant experiments showed that SCL does not affect the long-term repopulating capacity of HSCs but that WT- 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 into the lymphoid lineage. We conclude that the upregulation or downregulation of SCL directs an HSC toward myeloid or lymphoid lineage, respectively, although SCL does not affect its long-term repopulating capacity.
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