抄録
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 δ (PPAR-δ)-fatty- acid oxidation (FAO) pathway for the maintenance of hematopoietic stem cells (HSCs). We have found that loss of PPAR-δ or inhibition of mitochondrial FAO induces loss of HSC maintenance, whereas treatment with PPAR-δ agonists improved HSC maintenance. PML exerts its essential role in HSC maintenance through regulation of PPAR signaling and FAO. Mechanistically, the PML-PPAR-δ-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-δ activation increased asymmetric cell division. Thus, our findings identify a metabolic switch for the control of HSC cell fate with potential therapeutic implications.
本文言語 | 英語 |
---|---|
ページ(範囲) | 1350-1358 |
ページ数 | 9 |
ジャーナル | Nature medicine |
巻 | 18 |
号 | 9 |
DOI | |
出版ステータス | 出版済み - 9月 2012 |
外部発表 | はい |
!!!All Science Journal Classification (ASJC) codes
- 生化学、遺伝学、分子生物学(全般)