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PMID: 25843708 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression.

Cell reports ·Vol. 11 ·No. 1 ·2015-04-07 ·Pages 137-48

Jiang W, Liu Y, Liu R, Zhang K, Zhang Y

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.

MeSH Terms
Cell Differentiation/genetics Cell Lineage/genetics Endoderm/growth & development,metabolism Gastrulation/genetics Gene Expression Regulation, Developmental Hepatocyte Nuclear Factor 3-beta/biosynthesis,genetics Humans Promoter Regions, Genetic RNA, Long Noncoding/biosynthesis Smad2 Protein/biosynthesis,genetics Transcriptome/genetics
Chemicals
FOXA2 protein, human RNA, Long Noncoding SMAD2 protein, human Smad2 Protein Hepatocyte Nuclear Factor 3-beta
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Jiang Wei
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: [email protected].
Liu Yuting
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.
Liu Rui
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
Zhang Kun
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
Zhang Yi
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: [email protected].
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Article Info
Journal
Cell reports
Abbr.
Cell Rep
ISSN
2211-1247
DOI
10.1016/j.celrep.2015.03.008
Email
[email protected]
[email protected]
Published
2015-04-07
Epub
2015-00-02
Pages
137-48
Language
English
Region
United States
NLM ID
101573691
PMCID
PMC7721200
Subset
IM
Grants
NIDDK NIH HHS · U01 DK089565 · United States
Howard Hughes Medical Institute · United States
NIDDK NIH HHS · U01-DK089565 · United States
Databases
GEO
GSE44875
External Links
PubMed source DOI: 10.1016/j.celrep.2015.03.008 PMC Full Text View journal details
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