Overlapping functions of Krüppel-like factor family members: targeting multiple transcription factors to maintain the naïve pluripotency of mouse embryonic stem cells

Kruppel-like factors (Klf) possess a pivotal role to maintain self-renewal of mouse embryonic stem cells (mESCs). The function of three Klf family members has been identified, which are suggested to largely overlap. For further dissection of their functions, we applied an inducible knockout system for these Klf family members and assessed the impacts of combinatorial loss-of-function. As a result, we confirmed that any single Klf family member was sufficient to support self-renewal, whereas the removal of all three compromised it. The activity of any single transcription factor except for a Klf family member was not sufficient to restore self-renewal of the triple-knockout mESCs. However, some particular combinations of transcription factors were capable of the restoration. The triple-knockout mESCs were successfully captured at primed state. These data indicate that the pivotal function of the Klf family member is transduced into the activation of multiple transcription factors in naive-state-specific manner.