SIRT1 is dispensable for function of hematopoietic stem cells in adult mice.
SIRT1 is an NAD(+)-dependent histone deacetylase implicated in the establishment of the primitive hematopoietic system during mouse embryonic development. However, investigation of the role of SIRT1 in adult hematopoiesis has been complicated by the high perinatal mortality of SIRT1-deficient mice (SIRT1(-/-)). We performed a comprehensive in vivo study of the hematopoietic stem cell (HSC) compartment in adult SIRT1(-/-) mice and show that, apart from anemia and leukocytosis in older mice, the production of mature blood cells, lineage distribution within hematopoietic organs, and frequencies of the most primitive HSC populations are comparable to those of wild-type littermate controls. Furthermore, we show that SIRT1-deficient BM cells confer stable long-term reconstitution in competitive repopulation and serial transplantation experiments. The results of the present study rule out an essential physiologic role for cell-autonomous SIRT1 signaling in the maintenance of the adult HSC compartment in mice.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Vid
V
Leko
Barbara
B
Varnum-Finney
Hongzhe
H
Li
Yansong
Y
Gu
David
D
Flowers
Cynthia
C
Nourigat
Irwin D
ID
Bernstein
Antonio
A
Bedalov
D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D016130:Immunophenotyping; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D056564:Sirtuin 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D015703:Antigens, CD; D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019009:Proto-Oncogene Proteins c-kit; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1