Stat3 promotes mitochondrial transcription and oxidative respiration during maintenance and induction of naive pluripotency
Betto, Riccardo M
Soriano, Maria E
The EMBO Journal
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Carbognin, E., Betto, R. M., Soriano, M. E., Smith, A., & Graziano, M. (2016). Stat3 promotes mitochondrial transcription and oxidative respiration during maintenance and induction of naive pluripotency. The EMBO Journal, 35 618-634. https://doi.org/10.15252/embj.201592629
Transcription factor Stat3 directs self‐renewal of pluripotent mouse embryonic stem (ES) cells downstream of the cytokine leukemia inhibitory factor (LIF). Stat3 upregulates pivotal transcription factors in the ES cell gene regulatory network to sustain naïve identity. Stat3 also contributes to the rapid proliferation of ES cells. Here, we show that Stat3 increases the expression of mitochondrial‐encoded transcripts and enhances oxidative metabolism. Chromatin immunoprecipitation reveals that Stat3 binds to the mitochondrial genome, consistent with direct transcriptional regulation. An engineered form of Stat3 that localizes predominantly to mitochondria is sufficient to support enhanced proliferation of ES cells, but not to maintain their undifferentiated phenotype. Furthermore, during reprogramming from primed to naïve states of pluripotency, Stat3 similarly upregulates mitochondrial transcripts and facilitates metabolic resetting. These findings suggest that the potent stimulation of naïve pluripotency by LIF/Stat3 is attributable to parallel and synergistic induction of both mitochondrial respiration and nuclear transcription factors.
GM’s laboratory is supported by grants from Armenise-Harvard Foundation and Telethon Foundation (TCP13013). The Cambridge Stem Cell Institute receives core funding from the Wellcome Trust and Medical Research Council. GM was supported by a Human Frontier Science Program Fellowship. AS is a Medical Research Professor.
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External DOI: https://doi.org/10.15252/embj.201592629
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253489