TY - JOUR
T1 - Adult Hematopoietic Stem and Progenitor Cells Require Either Lyl1 or Scl for Survival
AU - Souroullas, George P.
AU - Salmon, Jessica M.
AU - Sablitzky, Fred
AU - Curtis, David J.
AU - Goodell, Margaret A.
N1 - Funding Information:
We thank Corinne Sonnet for assistance with mice; Dean Hewish for cell sorting; Jason Corbin for blood counts; and Lan Ta, Rebecca Bowyer, and Jenny Davis for animal husbandry. We also thank Fernando Camargo (MIT) for discussions that led to this study. This work was supported by National Health & Medical Research Council (NHMRC) project grant 332502. D.J.C. is supported by a NHMRC RD Wright Fellowship 382904. This work was also supported by NIH grants DK58192, EB005173, and HL08100.
PY - 2009/2/6
Y1 - 2009/2/6
N2 - 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.
AB - 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.
KW - STEMCELL
UR - http://www.scopus.com/inward/record.url?scp=58949098459&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2009.01.001
DO - 10.1016/j.stem.2009.01.001
M3 - Article
C2 - 19200805
AN - SCOPUS:58949098459
SN - 1934-5909
VL - 4
SP - 180
EP - 186
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 2
ER -