Long non-coding RNAs (lncRNAs) regulate diverse biological processes, including cell lineage specification. Here, researchers from Harvard Medical School report transcriptome profiling of human endoderm and pancreatic cell lineages using purified cell populations. Analysis of the data sets allows us to identify hundreds of lncRNAs that exhibit differentiation-stage-specific expression patterns. As a first step in characterizing these lncRNAs, they focus on an endoderm-specific lncRNA, definitive endoderm-associated lncRNA1 (DEANR1), and demonstrate that it plays an important role in human endoderm differentiation. DEANR1 contributes to endoderm differentiation by positively regulating expression of the endoderm factor FOXA2. Importantly, overexpression of FOXA2 is able to rescue endoderm differentiation defects caused by DEANR1 depletion. Mechanistically, DEANR1 facilitates FOXA2 activation by facilitating SMAD2/3 recruitment to the FOXA2 promoter. Thus, this study not only reveals a large set of differentiation-stage-specific lncRNAs but also characterizes a functional lncRNA that is important for endoderm differentiation.
- Jiang W, Liu Y, Liu R, Zhang K, Zhang Y. (2015) The lncRNA DEANR1 Facilitates Human Endoderm Differentiation by Activating FOXA2 Expression. Cell Rep [Epub ahead of print]. [article]