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GLP-1 Notch-LAG-1 CSL control of the germline stem cell fate is mediated by transcriptional targets lst-1 and sygl-1.
PLOS Genetics ( IF 4.0 ) Pub Date : 2020-03-20 , DOI: 10.1371/journal.pgen.1008650 Jian Chen 1 , Ariz Mohammad 1 , Nanette Pazdernik 1, 2 , Huiyan Huang 3 , Beth Bowman 4, 5 , Eric Tycksen 6 , Tim Schedl 1
PLOS Genetics ( IF 4.0 ) Pub Date : 2020-03-20 , DOI: 10.1371/journal.pgen.1008650 Jian Chen 1 , Ariz Mohammad 1 , Nanette Pazdernik 1, 2 , Huiyan Huang 3 , Beth Bowman 4, 5 , Eric Tycksen 6 , Tim Schedl 1
Affiliation
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Stem cell systems are essential for the development and maintenance of polarized tissues. Intercellular signaling pathways control stem cell systems, where niche cells signal stem cells to maintain the stem cell fate/self-renewal and inhibit differentiation. In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. We undertook a comprehensive genome-wide approach to identify transcriptional targets of GLP-1 signaling. We expected primary response target genes to be evident at the intersection of genes identified as directly bound by LAG-1, from ChIP-seq experiments, with genes identified as requiring GLP-1 signaling for RNA accumulation, from RNA-seq analysis. Furthermore, we performed a time-course transcriptomics analysis following auxin inducible degradation of LAG-1 to distinguish between genes whose RNA level was a primary or secondary response of GLP-1 signaling. Surprisingly, only lst-1 and sygl-1, the two known target genes of GLP-1 in the germline, fulfilled these criteria, indicating that these two genes are the primary response targets of GLP-1 Notch and may be the sole germline GLP-1 signaling protein-coding transcriptional targets for mediating the stem cell fate. In addition, three secondary response genes were identified based on their timing following loss of LAG-1, their lack of a LAG-1 ChIP-seq peak and that their glp-1 dependent mRNA accumulation could be explained by a requirement for lst-1 and sygl-1 activity. Moreover, our analysis also suggests that the function of the primary response genes lst-1 and sygl-1 can account for the glp-1 dependent peak protein accumulation of FBF-2, which promotes the stem cell fate and, in part, for the spatial restriction of elevated LAG-1 accumulation to the stem cell region.
中文翻译：
种系干细胞命运的GLP-1 Notch-LAG-1 CSL控制由转录靶lst-1和sygl-1介导。
干细胞系统对于极化组织的发育和维持至关重要。细胞间的信号通路控制着干细胞系统，其中利基细胞向干细胞发出信号以维持干细胞的命运/自我更新并抑制分化。在秀丽隐杆线虫种系中，GLP-1 Notch信号通过使用序列特异性DNA结合蛋白LAG-1来实现转录应答，从而确定了干细胞的命运。我们进行了全面的全基因组方法来识别GLP-1信号转导的转录目标。我们期望主要反应靶基因在来自ChIP-seq实验的被LAG-1直接结合的基因与来自RNA-seq分析的被鉴定为需要GLP-1信号进行RNA积累的基因的交点处明显。此外，我们在生长素诱导的LAG-1降解后进行了时程转录组学分析，以区分其RNA水平是GLP-1信号主要或次要反应的基因。出乎意料的是，只有lst-1和sygl-1（种系中GLP-1的两个已知靶基因）满足了这些标准，表明这两个基因是GLP-1 Notch的主要反应靶标，并且可能是唯一的种系GLP -1信号蛋白编码的转录靶标，介导干细胞命运。此外，根据其丢失LAG-1的时间，缺少LAG-1 ChIP-seq峰以及它们的glp-1依赖性mRNA积累可以鉴定出三个次级反应基因，这可以通过对lst-1的要求来解释。和sygl-1活动。此外，
更新日期：2020-04-06
中文翻译：
种系干细胞命运的GLP-1 Notch-LAG-1 CSL控制由转录靶lst-1和sygl-1介导。
干细胞系统对于极化组织的发育和维持至关重要。细胞间的信号通路控制着干细胞系统，其中利基细胞向干细胞发出信号以维持干细胞的命运/自我更新并抑制分化。在秀丽隐杆线虫种系中，GLP-1 Notch信号通过使用序列特异性DNA结合蛋白LAG-1来实现转录应答，从而确定了干细胞的命运。我们进行了全面的全基因组方法来识别GLP-1信号转导的转录目标。我们期望主要反应靶基因在来自ChIP-seq实验的被LAG-1直接结合的基因与来自RNA-seq分析的被鉴定为需要GLP-1信号进行RNA积累的基因的交点处明显。此外，我们在生长素诱导的LAG-1降解后进行了时程转录组学分析，以区分其RNA水平是GLP-1信号主要或次要反应的基因。出乎意料的是，只有lst-1和sygl-1（种系中GLP-1的两个已知靶基因）满足了这些标准，表明这两个基因是GLP-1 Notch的主要反应靶标，并且可能是唯一的种系GLP -1信号蛋白编码的转录靶标，介导干细胞命运。此外，根据其丢失LAG-1的时间，缺少LAG-1 ChIP-seq峰以及它们的glp-1依赖性mRNA积累可以鉴定出三个次级反应基因，这可以通过对lst-1的要求来解释。和sygl-1活动。此外，
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