Adult hematopoietic stem and progenitor cells require either Lyl1 or Scl for survival.
Scl and Lyl1 encode two related basic-helix-loop-helix transcription factors implicated in T cell acute lymphoblastic leukemia. Previous studies showed that Scl is essential for embryonic and adult erythropoiesis, while Lyl1 is important for B cell development. Single-knockout mice have not revealed an essential function for Scl or Lyl1 in adult hematopoietic stem cells (HSCs). To determine if maintenance of HSCs in single-knockout mice is due to functional redundancy, we generated Lyl1;Scl-conditional double-knockout mice. Here, we report a striking genetic interaction between the two genes, with a clear dose dependence for the presence of Scl or Lyl1 alleles for HSC function. Bone marrow repopulation assays and analyses demonstrated rapid loss of hematopoietic progenitors due to apoptosis. The function of HSCs could be rescued by a single allele of Lyl1 but not Scl. These results show that expression of at least one of these factors is essential for maintenance of adult HSC function.
Souroullas
George P
GP
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Salmon
Jessica M
JM
Sablitzky
Fred
F
Curtis
David J
DJ
Goodell
Margaret A
MA
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C490130:Lyl1 protein, mouse; C489366:Tal1 protein, mouse