Hoxa1-regulated Long Noncoding RNAs in Regulating Retinoic Acid-induced ESCs Early Differentiation. Mus musculus strain:129/Ola

Although the functional roles of Hoxa1 have been increasingly identified, whether lncRNAs regulated by Hoxa1 involving retinoic acid (RA)-induced embryonic stem cells (ESCs) early differentiation is not clear. Here, by combining Hoxa1-ChIP-seq with RNA-seq data after ESCs differentiation induced by RA, we found that seven lncRNAs expression were significantly correlated with Hoxa1. Overexpression or deletion of Hoxa1 showed that four lncRNAs (Hotairm1, Hoxaas2, Halr1, Gas5) were directly regulated by Hoxa1. Furthermore, CRISPR/Cas9-mediated deletion or depletion of the four lncRNAs shown that various signaling pathways are activated or inhibited (such as retinol metabolism and PPAR signaling pathways) , which significantly influences the proper differentiation of ESCs induced by RA. Our results demonstrate that Hoxa1-regulated lncRNAs play an important role in RA-induced ESCs early differentiation through maintaining the target signal pathways, which may enhance our understanding of the molecular basis during ESCs early differentiation.