A PML–PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance
- PMID: 22902876
- PMCID: PMC3566224
- DOI: 10.1038/nm.2882
A PML–PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance
Abstract
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.
Conflict of interest statement
The authors declare no competing financial interests.
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Comment in
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A ROSy future for metabolic regulation of HSC division.Nat Med. 2012 Sep;18(9):1334-6. doi: 10.1038/nm.2917. Nat Med. 2012. PMID: 22961159 No abstract available.
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Fate through fat: lipid metabolism determines stem cell division outcome.Cell Metab. 2012 Oct 3;16(4):411-3. doi: 10.1016/j.cmet.2012.09.011. Cell Metab. 2012. PMID: 23040066 Free PMC article.
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Hematopoietic stem cells burn fat to prevent exhaustion.Cell Stem Cell. 2012 Oct 5;11(4):447-9. doi: 10.1016/j.stem.2012.09.008. Cell Stem Cell. 2012. PMID: 23040473
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