Stem cell leukemia protein directs hematopoietic stem cell fate.
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.
Kunisato
Atsushi
A
Department of Hematology/Oncology, Graduate School of Medicine, University of Tokyo, Japan.
Chiba
Shigeru
S
Saito
Toshiki
T
Kumano
Keiki
K
Nakagami-Yamaguchi
Etsuko
E
Yamaguchi
Tomoyuki
T
Hirai
Hisamaru
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005333:Fetus; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology*; D009924:Organ Culture Techniques; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013950:Thymus Gland; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C489366:Tal1 protein, mouse