| First Author | Kinder M | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 24 | Pages | 5012-22 |
| PubMed ID | 20357242 | Mgi Jnum | J:161545 |
| Mgi Id | MGI:4459596 | Doi | 10.1182/blood-2009-09-243139 |
| Citation | Kinder M, et al. (2010) Hematopoietic stem cell function requires 12/15-lipoxygenase-dependent fatty acid metabolism. Blood 115(24):5012-22 |
| abstractText | Fatty acid metabolism governs multiple intracellular signaling pathways in many cell types, but its role in hematopoietic stem cells (HSCs) is largely unknown. Herein, we establish a critical role for 12/15-lipoxygenase (12/15-LOX)-mediated unsaturated fatty acid metabolism in HSC function. HSCs from 12/15-LOX-deficient mice are severely compromised in their capacity to reconstitute the hematopoietic compartment in competitive and serial reconstitution assays. Furthermore, we demonstrate that 12/15-LOX is required for the maintenance of long-term HSC quiescence and number. The defect in HSCs is cell-autonomous and associated with a selective reduction in 12/15-LOX-mediated generation of bioactive lipid mediators and reactive oxygen species and with a decrease in canonical Wnt signaling as measured by nuclear beta-catenin staining. These results have implications for development, aging, and transformation of the hematopoietic compartment. |
