Klf14 is an imprinted transcription factor that regulates placental growth.
Klf14 is an imprinted transcription factor that regulates placental growth.
复制标题
DOI：
10.1016/j.placenta.2019.09.013
复制
发表时间：
2019-12
期刊：
影响因子：
3.8
通讯作者：
Chaillet JR
中科院分区：
文献类型：
--
作者：
Koppes E;Shaffer B;Sadovsky E;Himes K;Barak Y;Sadovsky Y;Chaillet JR
印迹基因优先从一个亲本遗传等位基因表达，其中许多对胎盘功能和胎儿生长的调节至关重要。小鼠kr<s:1> ppel样因子14 （Klf14）是母系表达的印迹转录因子，是小鼠6号染色体上Mest印迹基因簇的一个组成部分。我们试图确定Klf14表达的缺失是否会改变正常小鼠的胚胎外发育过程。我们还使用高通量RNA测序（RNAseq）在Klf14缺失的胎盘中鉴定了一组差异表达基因（DEGs）。我们使用重组和转基因方法产生了Klf14敲除（Klf14null）小鼠。为了鉴定小鼠胎盘中的deg，我们通过RNAseq比较了来自17.5dpc Klf14matKO和野生型窝偶胎盘的mRNA转录组。在Klf14matKO匹配的男性和女性胎龄独立队列中，用定量反转录PCR （qPCR）证实了候选deg。我们发现17.5%的胎盘遗传了母体零等位基因（Klf14matKO），具有适度的过度生长表型，Klf14的表达几乎完全消失。然而，对胎儿生长没有影响。我们通过RNAseq鉴定了Klf14matKO胎盘中20个差异表达的deg，随后通过qPCR验证了5个高度上调的deg （Begain, Col26a1, Fbln5， Gdf10和Nell1）。最丰富的功能基因网络包括那些被归类为调节细胞发育和代谢的基因。这些结果表明，小鼠胎盘中母体Klf14位点的缺失会导致调节胎盘生长的基因表达模式的改变。
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 (Klf14) is a maternally expressed imprinted transcription factor that is a component of the Mest imprinted gene cluster on mouse chromosome 6. We sought to determine if loss of Klf14 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 Klf14. We generated a Klf14 knockout (Klf14null) mouse using recombineering and transgenic approaches. To identify DEGs in the mouse placenta we compared mRNA transcriptomes derived from 17.5dpc Klf14matKO 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 Klf14matKO placentas. We found that 17.5dpc placentas inheriting a maternal null allele (Klf14matKO) had a modest overgrowth phenotype and a near complete ablation of Klf14 expression. However, there was no effect on fetal growth. We identified 20 DEGs differentially expressed in Klf14matKO placentas by RNAseq, and subsequently validated five that are highly upregulated (Begain, Col26a1, Fbln5, Gdf10, and Nell1) by qPCR. The most enriched functional gene-networks included those classified as regulating cellular development and metabolism. These results suggest that loss of the maternal Klf14 locus in the mouse placenta acts results in changes in gene expression patterns that modulate placental growth.
登录
查看更多内容
影响因子：
3.8
作者：
Himes, K. P.;Young, A.;Koppes, E.;Stolz, D.;Barak, Y.;Sadovsky, Y.;Chaillet, J. R.
通讯作者：
Chaillet, J. R.
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
2.9
作者：
Barak Y;Sadovsky Y;Shalom-Barak T
通讯作者：
Shalom-Barak T
影响因子：
3.7
作者：
Koppes E;Himes KP;Chaillet JR
通讯作者：
Chaillet JR
KLF14 缺失会触发中心体扩增和肿瘤发生
影响因子：
16.6
作者：
Fan G;Sun L;Shan P;Zhang X;Huan J;Zhang X;Li D;Wang T;Wei T;Zhang X;Gu X;Yao L;Xuan Y;Hou Z;Cui Y;Cao L;Li X;Zhang S;Wang C
通讯作者：
Wang C