SIRT1 is dispensable for function of hematopoietic stem cells in adult mice.

Publication Type:

Journal Article

Source:

Blood, Volume 119, Issue 8, p.1856-1860 (2012)

Keywords:

2012, Center-Authored Paper, Clinical Research Division, Comparative Medicine Core Facility, Experimental Histopathology Core Facility, Flow Cytometry Core Facility, Genomics Core Facility, Jan 12, January 2012, Scientific Imaging Core Facility, Shared Resources

Abstract:

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 high perinatal mortality of SIRT1-deficient mice (SIRT1(-/-)). Herein we perform a comprehensive in vivo study of the hematopoietic stem cell (HSC) compartment in adult SIRT1(-/-) animals and show that, apart from anemia and leukocytosis in older mice, 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 bone marrow cells confer stable long-term reconstitution in competitive repopulation and serial transplantation experiments. Taken together, our results rule out an essential physiological role for cell-autonomous SIRT1 signaling in maintenance of adult HSC compartment in the mouse.