To determine if lincRNAs act in repressing differentiation programs we compared the overall gene expression patterns resulting from knockdown of the lincRNAs to published gene expression patterns resulting from induced differentiation of ESCs32,33 and assessed significance using a permutation-derived FDR34 (see Methods). These states include differentiation into endoderm, ectoderm, neuroectoderm, mesoderm, and trophectoderm lineages. As a positive control for our analytical method, we confirmed the expected results that the expression pattern caused by Oct4 knockdown was strongly associated with the trophoectoderm lineage35 and the pattern caused by Nanog knockdown was strongly associated with endoderm differentiation30 (Figure 3a).
