Klf14 is an imprinted transcription factor that regulates placental growth

Abstract

<div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="title" id="d1367342e160">Introduction:</h5> <p id="P1">Imprinted genes are preferentially expressed from one parentally inherited allele, and many are crucial to the regulation of placental function and fetal growth. Murine Krüppel-like factor 14 ( <i>Klf14</i>) is a maternally expressed imprinted transcription factor that is a component of the <i>Mest</i> imprinted gene cluster on mouse chromosome 6. We sought to determine if loss of <i>Klf14</i> expression alters the course of normal mouse extraembryonic development. We also used high-throughput RNA sequencing (RNAseq) to identify a set of differentially expressed genes (DEGs) in placentas with loss of <i>Klf14</i>. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="title" id="d1367342e177">Methods:</h5> <p id="P2">We generated a <i>Klf14</i> knockout ( <i>Klf14</i> ^<i>null</i>) mouse using recombineering and transgenic approaches. To identify DEGs in the mouse placenta we compared mRNA transcriptomes derived from 17.5dpc <i>Klf14</i> ^<i>matKO</i> and wild-type littermate placentas by RNAseq. Candidate DEGs were confirmed with quantitative reverse transcription PCR (qPCR) on an independent cohort of male and female gestational age matched <i>Klf14</i> ^<i>matKO</i> placentas. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="title" id="d1367342e213">Results:</h5> <p id="P3">We found that 17.5dpc placentas inheriting a maternal null allele ( <i>Klf14</i> ^matKO) had a modest overgrowth phenotype and a near complete ablation of <i>Klf14</i> expression. However, there was no effect on fetal growth. We identified 20 DEGs differentially expressed in <i>Klf14</i> ^matKO placentas by RNAseq, and subsequently validated five that are highly upregulated ( <i>Begain</i>, <i>Col26a1</i>, <i>Fbln5</i>, <i>Gdf10</i>, and <i>Nell1</i>) by qPCR. The most enriched functional gene-networks included those classified as regulating cellular development and metabolism. </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="title" id="d1367342e249">Conclusion:</h5> <p id="P4">These results suggest that loss of the maternal <i>Klf14</i> locus in the mouse placenta acts results in changes in gene expression patterns that modulate placental growth. </p> </div>