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 C. elegans, GLP-1 Notch signaling specifies the germline stem cell fate and inhibits meiotic development, employing the sequence-specific DNA binding protein LAG-1 to initiate the transcriptional response. We undertook a comprehensive genome-wide approach to identify transcriptional targets of GLP-1 signaling. We expected primary targets to (a) be directly bound by LAG-1 in the germline observed through ChIP-seq experiments, and (b) require GLP-1 signaling for their RNA accumulation in dissected germlines based on RNA-seq analysis. Furthermore, we have shown that all stem cells switch to meiotic development in response to germline autonomous auxin inducible degradation of LAG-1 or GLP-1. We therefore 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. Thus far, we have identified
lst-1 and
sygl-1 as two genes that fulfilled these criteria, consistent with their known function to promote 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.