The fact that knockdown of these 30 lincRNAs induces gene expression programs associated with specific early differentiation lineages suggests that these lincRNAs normally are a barrier to such differentiation. Interestingly, most of the lincRNA knockdowns (~85%) that induce gene expression patterns associated with these lineages did not cause the cells to differentiate as determined by Nanog reporter levels (Supplemental Table 7) and Oct4 expression (Supplemental Figure 10). This is consistent with observations for several critical ESC chromatin regulators, such as the polycomb complex; loss-of-function of these regulators similarly induce lineage-specific markers without causing differentiation18,36,37.
