10.1371/journal.pone.0150715

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

Abstract

<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

Similar works

Full text

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

This paper was published in FigShare.

Having an issue?

Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.