| First Author | Ou X | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 2 | Pages | 440-50 |
| PubMed ID | 20966168 | Mgi Jnum | J:168412 |
| Mgi Id | MGI:4888174 | Doi | 10.1182/blood-2010-03-273011 |
| Citation | Ou X, et al. (2011) SIRT1 deficiency compromises mouse embryonic stem cell hematopoietic differentiation, and embryonic and adult hematopoiesis in the mouse. Blood 117(2):440-50 |
| abstractText | SIRT1 is a founding member of a sirtuin family of 7 proteins and histone deacetylases. It is involved in cellular resistance to stress, metabolism, differentiation, aging, and tumor suppression. SIRT1(-/-) mice demonstrate embryonic and postnatal development defects. We examined hematopoietic and endothelial cell differentiation of SIRT1(-/-) mouse embryonic stem cells (ESCs) in vitro, and hematopoietic progenitors in SIRT1(+/+)(+/-), and (-/-) mice. SIRT1(-/-) ESCs formed fewer mature blast cell colonies. Replated SIRT1(-/-) blast colony-forming cells demonstrated defective hematopoietic potential. Endothelial cell production was unaltered, but there were defects in formation of a primitive vascular network from SIRT1(-/-)-derived embryoid bodies. Development of primitive and definitive progenitors derived from SIRT1(-/-) ESCs were also delayed and/or defective. Differentiation delay/defects were associated with delayed capacity to switch off Oct4, Nanog and Fgf5 expression, decreased beta-H1 globin, beta-major globin, and Scl gene expression, and reduced activation of Erk1/2. Ectopic expression of SIRT1 rescued SIRT1(-/-) ESC differentiation deficiencies. SIRT1(-/-) yolk sacs manifested fewer primitive erythroid precursors. SIRT1(-/-) and SIRT1(+/-) adult marrow had decreased numbers and cycling of hematopoietic progenitors, effects more apparent at 5%, than at 20%, oxygen tension, and these progenitors survived less well in vitro under conditions of delayed growth factor addition. This suggests a role for SIRT1 in ESC differentiation and mouse hematopoiesis. |
