The pluripotent state is governed by transcription factor networks in which each factor is reciprocally regulated to maintain its balanced expression. Three Kruppel-like factor (Klf) genes, Klf2, Klf4 and Klf5 have each been implicated in the network, but combined, complete loss-of-function studies have not yet been performed to assess their function in mouse embryonic stem cells (mESCs). Now, Hitoshi Niwa and colleagues apply a combinatorial inducible knockout strategy and chimeric embryo assays to definitively prove that Klf2, Klf4 and Klf5 share overlapping functions and that neither Klf2 nor Klf4 are essential for the maintenance of pluripotency in mESCs. Their results reveal an immediate early reduction in the naïve pluripotency factors Nanog, Esrrb, Tbx3 and others, followed by a more gradual loss of the general pluripotency-associated factors Oct3/4 and Sox2. The authors then screened other members of the Klf family for their ability to maintain pluripotency in the triple Klf2/4/5 knockout mESCs and identified only one member, Klf17, that showed a partial rescue effect. This is interesting, as Klf17 expression is negligible in mESCs, and KLF17 expression has been reported in the epiblast of the human pre-implantation embryos and also in human naïve-like PSCs. The findings presented by Niwa and colleagues are important for our understanding of the transcription factor network that governs pluripotency and the redundancy that exists within it.
Transcription factor networks in mammalian pluripotency: the case for Klfs
Transcription factor networks in mammalian pluripotency: the case for Klfs. Development 15 May 2018; 145 (10): e1006. doi:
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