Regulatory Role of Klf5 in Early Mouse Development and in Embryonic Stem Cells

Pluripotency and self-renewal of embryonic stem cells (ESCs) are maintained by regulatory mechanisms, based on a sophisticated network of transcription factors. Recently, a growing body of evidence has indicated that Klf5, a transcription factor highly expressed in mouse ESCs and during the early phases of mouse development, plays a crucial role in maintaining ESC self-renewal and pluripotency, in governing ESC fate decisions and proper development of blastocyst in vivo. Indeed, Klf5-null mice show developmental defects at blastocyst stage, due to the defective establishment of the inner cell mass. Moreover, Klf5 knockdown in ESCs results in the loss of undifferentiated phenotype, whereas its ectopic expression is sufficient to maintain ESC in the undifferentiated state, even in the absence of LIF. Finally, it has been recently reported that Klf5 activates the expression of self-renewal-promoting genes and, simultaneously, it inhibits the expression of differentiation-related genes. Here, we discuss the functional role of Klf5 in the control on ESC self-renewal and pluripotency and its integration in the core transcriptional network governing ESC state.