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Δευτέρα 28 Αυγούστου 2017

The transcription factor Gbx2 induces expression of Kruppel-like factor 4 to maintain and induce naive pluripotency of embryonic stem cells [Developmental Biology]

The transcription factor gastrulation brain homeobox 2 (Gbx2) is a direct target of the LIF/STAT3 signaling pathway, maintains mouse embryonic stem cell (mESC) self-renewal, and facilitates mouse epiblast stem cell (mEpiSC) reprogramming to naive pluripotency. However, the mechanism by which Gbx2 mediates its effects on pluripotency remains unknown. Here, using an RNA-Seq approach, we identified Kruppel-like factor (Klf4) as a direct target of Gbx2. Functional studies indicated that Klf4 mediates the self-renewal-promoting effects of Gbx2, as knockdown of Klf4 expression abrogated the ability of Gbx2 to maintain the undifferentiated state of mESCs. We also found that Gbx2 largely depends on Klf4 to reprogram mEpiSCs to a mESC-like state. In summary, our study has uncovered a mechanism by which Gbx2 maintains and induces naive pluripotency. These findings expand our understanding of the pluripotency control network and may inform the development of culture conditions for improved ESC maintenance and differentiation.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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