Loss of Krüppel-like factor 9 deregulates both physiological gene expression and development.
Loss of Krüppel-like factor 9 deregulates both physiological gene expression and development.
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DOI：
10.1038/s41598-023-39453-3
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发表时间：
2023-07-28
影响因子：
4.6
通讯作者：
Coffman, James A.
中科院分区：
文献类型：
--
作者：
Drepanos, Laura;Gans, Ian M.;Grendler, Janelle;Guitar, Sophia;Fuqua, J. Heath;Maki, Nathaniel J.;Tilden, Andrea R.;Graber, Joel H.;Coffman, James A.
KRüppel-like factor9(KLF9)是一种广泛表达的转录因子，是多种应激反应和内分泌信号通路的前馈调节因子。我们先前描述了Klf9功能的丧失如何影响受精后5天(DPF)单个时间点采集的斑马鱼幼体的转录组。然而，KLF9的表达呈昼夜振荡，采样时间点与其表达的最低点相对应。为了确定KLF9−/−突变的转录效应是否随着一天中的不同时间而变化，我们对在黎明前KLF9表达高峰期和上午10点左右的三个时间点采样的5个DPF斑马鱼胚胎进行了批量RNASEQ。我们发现，虽然我们之前报道的KLF9−/−突变的主要影响对一天的时间很强，但该突变还有额外的影响，只在黎明前的时间点表现出来。我们使用一份已出版的斑马鱼发育的单细胞图谱，将KLF9基因突变对不同细胞类型的影响联系起来，发现该突变增加了与消化器官(肝脏、胰腺和肠道)相关的−/−，减少了与神经元和血液分化相关的基因。来自共焦成像的幼虫的测量表明，KLF9−/−突变体中肝脏基因的过度表达是由于肝脏增大所致。
Krüppel-like factor 9 (Klf9) is a ubiquitously expressed transcription factor that is a feedforward regulator of multiple stress-responsive and endocrine signaling pathways. We previously described how loss of Klf9 function affects the transcriptome of zebrafish larvae sampled at a single time point 5 days post-fertilization (dpf). However, klf9 expression oscillates diurnally, and the sampled time point corresponded to its expression nadir. To determine if the transcriptomic effects of the klf9−/− mutation vary with time of day, we performed bulk RNA-seq on 5 dpf zebrafish embryos sampled at three timepoints encompassing the predawn peak and midmorning nadir of klf9 expression. We found that while the major effects of the klf9−/− mutation that we reported previously are robust to time of day, the mutation has additional effects that manifest only at the predawn time point. We used a published single-cell atlas of zebrafish development to associate the effects of the klf9−/− mutation with different cell types and found that the mutation increased mRNA associated with digestive organs (liver, pancreas, and intestine) and decreased mRNA associated with differentiating neurons and blood. Measurements from confocally-imaged larvae suggest that overrepresentation of liver mRNA in klf9−/− mutants is due to development of enlarged livers.
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