NANOG amplifies STAT3 activation and they synergistically induce the naïve pluripotent program

Naïve pluripotent stem cells have the ability to differentiate into any cell of an adult organism, and thus hold great promise for drug development and regenerative medicine. Such cells can be obtained directly from the embryo, or by reprogramming of a differentiated cell back to a naïve pluripotent identity. In this study, we connect NANOG with STAT3 signalling, two key mechanisms driving naïve pluripotency acquisition. Our finding that NANOG modulates signal transduction of extracellular cues adds a new dimension to the interplay between external environment and nuclear control networks to instate and reinforce cellular identity.

Publication details:

Stuart HT, van Oosten AL, Radzisheuskaya A, Martello G, Miller A, Dietmann S, Nichols J, Silva JC. NANOG Amplifies STAT3 Activation and They Synergistically Induce the Naive Pluripotent Program. Current Biology. PMID: 24462001

Full article in Current Biology

Image 3

Simplified schematic depicting the newfound role of NANOG in the modulation of LIF/STAT3 signal transduction. We discovered that NANOG represses Socs3 and amplifies STAT3 activation. Furthermore, we found that NANOG and STAT3 upregulate Klf4 in a co-dependent and synergistic manner. Functionally, STAT3 activation and KLF4 expression allowed us to bypass the requirement for NANOG in reprogramming.

Image credit: Hannah Stuart (first author)

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