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Stem Cells. 2016 Jan;34(1):83-92. doi: 10.1002/stem.2209. Epub 2015 Sep 29.

Srebp-1 Interacts with c-Myc to Enhance Somatic Cell Reprogramming.

Author information

1
Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People's Republic of China.
2
Peking Union Medical College, Program of Radiation Protection & Drug Discovery, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin, People's Republic of China.

Abstract

Somatic cell reprogramming is accompanied by changes in lipid metabolism. While attempting to dissect the molecular mechanisms of the lipid metabolic switch during reprogramming, we found that overexpression of sterol regulatory element binding protein-1 (Srebp-1), a transcriptional factor required for lipid homeostasis, enhances reprogramming efficiency, while knockdown or pharmaceutical inhibition of Srebp-1 is inhibitory. Srebp-1 overexpression blocks the formation of partially reprogrammed cells, and functions in the early phase of reprogramming. Furthermore, Srebp-1 functions in nucleus and depends on its transcriptional activity but not its ability to bind the E-box motif and regulation of canonical targets. Mechanistically, Srebp-1 interacts with c-Myc, facilitates its binding to downstream pluripotent targets, strengthens the function of c-Myc in enhancing other Yamanaka factors' binding, and thereby promotes the expression of pluripotent genes. These results elucidate a novel role for Srebp-1 in somatic cell reprogramming and provide insights into understanding the metabolic switch during reprogramming.

KEYWORDS:

C-Myc; Induced pluripotent stem cells; Metabolism; Reprogramming; Srebp-1

PMID:
26388522
DOI:
10.1002/stem.2209
[Indexed for MEDLINE]
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