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Author(s): Seung-Hoi Koo [1]; Hiroaki Satoh [2]; Stephan Herzig [1]; Chih-Hao Lee [3]; Susan Hedrick [1]; Rohit Kulkarni [4]; Ronald M Evans [3]; Jerrold Olefsky [2]; Marc Montminy (corresponding author) [...]

Author(s): Seung-Hoi Koo; Hiroaki Satoh; Stephan Herzig; Chih-Hao Lee; Susan Hedrick; Rohit Kulkarni; Ronald M Evans; Jerrold Olefsky; Marc Montminy Nature Medicine 10, 530-534 (2004) In the version of this [...]

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 ? (PPAR-?)-fatty-acid oxidation (FAO) pathway for the maintenance of hematopoietic stem cells (HSCs). We have found that loss of PPAR-? or inhibition of mitochondrial FAO induces loss of HSC maintenance, whereas treatment with PPAR-? agonists improved HSC maintenance. PML exerts its essential role in HSC maintenance through regulation of PPAR signaling and FAO. Mechanistically, the PML-PPAR-?-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-? activation increased asymmetric cell division. Thus, our findings identify a metabolic switch for the control of HSC cell fate with potential therapeutic implications. [ABSTRACT FROM AUTHOR]