| First Author | Ito K | Year | 2012 |
| Journal | Nat Med | Volume | 18 |
| Issue | 9 | Pages | 1350-8 |
| PubMed ID | 22902876 | Mgi Jnum | J:192771 |
| Mgi Id | MGI:5466461 | Doi | 10.1038/nm.2882 |
| Citation | Ito K, et al. (2012) A PML-PPAR-delta pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nat Med 18(9):1350-8 |
| abstractText | Stem-cell function is an exquisitely regulated process. Thus far, the contribution of metabolic cues to stem-cell function has not been well understood. Here we identify a previously unknown promyelocytic leukemia (PML)-peroxisome proliferator-activated receptor delta (PPAR-delta)-fatty-acid oxidation (FAO) pathway for the maintenance of hematopoietic stem cells (HSCs). We have found that loss of PPAR-delta or inhibition of mitochondrial FAO induces loss of HSC maintenance, whereas treatment with PPAR-delta agonists improved HSC maintenance. PML exerts its essential role in HSC maintenance through regulation of PPAR signaling and FAO. Mechanistically, the PML-PPAR-delta-FAO pathway controls the asymmetric division of HSCs. Deletion of Ppard or Pml as well as inhibition of FAO results in the symmetric commitment of HSC daughter cells, whereas PPAR-delta activation increased asymmetric cell division. Thus, our findings identify a metabolic switch for the control of HSC cell fate with potential therapeutic implications. |
