title: The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression.
abstract: Long non-coding RNAs (lncRNAs) regulate diverse biological processes, including cell lineage specification. Here, we 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, we 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, our study not only reveals a large set of differentiation-stage-specific lncRNAs but also characterizes a functional lncRNA that is important for endoderm differentiation.
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA. Electronic address: wei.jiang@childrens.harvard.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA. Electronic address: yzhang@genetics.med.harvard.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D004707:Endoderm / Q000254:growth & development / Q000378:metabolism; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051542:Hepatocyte Nuclear Factor 3-beta / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000096:biosynthesis*; D051899:Smad2 Protein / Q000096:biosynthesis* / Q000235:genetics; D059467:Transcriptome / Q000235:genetics
chemical_list: C496502:FOXA2 protein, human; D062085:RNA, Long Noncoding; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D051542:Hepatocyte Nuclear Factor 3-beta
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