Comprehensive Identification of <i>Krüppel-Like Factor</i> Family Members Contributing to the Self-Renewal of Mouse Embryonic Stem Cells and Cellular Reprogramming


<div><p>Pluripotency is maintained in mouse embryonic stem (ES) cells and is induced from somatic cells by the activation of appropriate transcriptional regulatory networks. <i>Krüppel-like factor</i> gene family members, such as <i>Klf2</i>, <i>Klf4</i> and <i>Klf5</i>, have important roles in maintaining the undifferentiated state of mouse ES cells as well as in cellular reprogramming, yet it is not known whether other <i>Klf</i> family members exert self-renewal and reprogramming functions when overexpressed. In this study, we examined whether overexpression of any representative <i>Klf</i> family member, such as <i>Klf1–Klf10</i>, would be sufficient for the self-renewal of mouse ES cells. We found that only <i>Klf2</i>, <i>Klf4</i>, and <i>Klf5</i> produced leukemia inhibitory factor (LIF)-independent self-renewal, although most KLF proteins, if not all, have the ability to occupy the regulatory regions of <i>Nanog</i>, a critical Klf target gene. We also examined whether overexpression of any of <i>Klf1-Klf10</i> would be sufficient to convert epiblast stem cells into a naïve pluripotent state and found that <i>Klf5</i> had such reprogramming ability, in addition to <i>Klf2</i> and <i>Klf4</i>. We also delineated the functional domains of the <i>Klf2</i> protein for LIF-independent self-renewal and reprogramming. Interestingly, we found that both the N-terminal transcriptional activation and C-terminal zinc finger domains were indispensable for this activity. Taken together, our comprehensive analysis provides new insight into the contribution of <i>Klf</i> family members to mouse ES self-renewal and cellular reprogramming.</p></div

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oai:figshare.com:article/3094849Last time updated on 2/12/2018

This paper was published in FigShare.

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